Niels Vejlstrup

ESC Guidelines on the management of cardiovascular diseases during pregnancy: the Task Force on the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology (ESC)

Table 1. Classes of recommendation Table 2. Levels of evidence Table 3. Estimated fetal and maternal effective doses for various diagnostic and interventional radiology procedures Table 4. Predictors of maternal cardiovascular events and risk score from the CARPREG study Table 5. Predictors of maternal cardiovascular events identified in congential heart diseases in the ZAHARA and Khairy study Table 6. Modified WHO classification of maternal cardiovascular risk: principles Table 7. Modified WHO classification of maternal cardiovascular risk: application Table 8. Maternal predictors of neonatal events in women with heart disease Table 9. General recommendations Table 10. Recommendations for the management of congenital heart disease Table 11. Recommendations for the management of aortic disease Table 12. Recommendations for the management of valvular heart disease Table 13. Recommendations for the management of coronary artery disease Table 14. Recommendations for the management of cardiomyopathies and heart failure Table 15. Recommendations for the management of arrhythmias Table 16. Recommendations for the management of hypertension Table 17. Check list for risk factors for venous thrombo-embolism Table 18. Prevalence of congenital thrombophilia and the associated risk of venous thrombo-embolism during pregnancy Table 19. Risk groups according to risk factors: definition and preventive measures Table 20. Recommendations for the prevention and management of venous thrombo-embolism in pregnancy and puerperium Table 21. Recommendations for drug use ABPM : ambulatory blood pressure monitoring ACC : American College of Cardiology ACE : angiotensin-converting enzyme ACS : acute coronary syndrome AF : atrial fibrillation AHA : American Heart Association aPTT : activated partial thromboplastin time ARB : angiotensin receptor blocker AS : aortic stenosis ASD : atrial septal defect AV : atrioventricular AVSD : atrioventricular septal defect BMI : body mass index BNP : B-type natriuretic peptide BP : blood pressure CDC : Centers for Disease Control CHADS : congestive heart failure, hypertension, age (>75 years), diabetes, stroke CI : confidence interval CO : cardiac output CoA : coarction of the aorta CT : computed tomography CVD : cardiovascular disease DBP : diastolic blood pressure DCM : dilated cardiomyopathy DVT : deep venous thrombosis ECG : electrocardiogram EF : ejection fraction ESC : European Society of Cardiology ESH : European Society of Hypertension ESICM : European Society of Intensive Care Medicine FDA : Food and Drug Administration HCM : hypertrophic cardiomyopathy ICD : implantable cardioverter-defibrillator INR : international normalized ratio i.v. : intravenous LMWH : low molecular weight heparin LV : left ventricular LVEF : left ventricular ejection fraction LVOTO : left ventricular outflow tract obstruction MRI : magnetic resonance imaging MS : mitral stenosis NT-proBNP : N-terminal pro B-type natriuretic peptide NYHA : New York Heart Association OAC : oral anticoagulant PAH : pulmonary arterial hypertension PAP : pulmonary artery pressure PCI : percutaneous coronary intervention PPCM : peripartum cardiomyopathy PS : pulmonary valve stenosis RV : right ventricular SBP : systolic blood pressure SVT : supraventricular tachycardia TGA : complete transposition of the great arteries TR : tricuspid regurgitation UFH : unfractionated heparin VSD : ventricular septal defect VT : ventricular tachycardia VTE : venous thrombo-embolism WHO : World Health Organization Guidelines summarize and evaluate all available evidence, at the time of the writing process, on a particular issue with the aim of assisting physicians in selecting the best management strategies for an individual patient, with a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are no substitutes but are complements for textbooks and cover the European Society of Cardiology (ESC) Core Curriculum topics. Guidelines and recommendations should help the …

Exenatide reduces reperfusion injury in patients with ST-segment elevation myocardial infarction.

AIMS Exenatide, a glucagon-like-peptide-1 analogue, increases myocardial salvage in experimental settings with coronary occlusion and subsequent reperfusion. We evaluated the cardioprotective effect of exenatide at the time of reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). METHODS AND RESULTS A total of 172 patients with STEMI and Thrombolysis in Myocardial Infarction flow 0/1 were randomly assigned to exenatide or placebo (saline) intravenously. Study treatment was commenced 15 min before intervention and maintained for 6 h after the procedure. The primary endpoint was salvage index calculated from myocardial area at risk (AAR), measured in the acute phase, and final infarct size measured 90 ± 21 days after pPCI by cardiac magnetic resonance (CMR). In 105 patients evaluated with CMR, a significantly larger salvage index was found in the exenatide group than in the placebo group (0.71 ± 0.13 vs. 0.62 ± 0.16; P= 0.003). Infarct size in relation to AAR was also smaller in the exenatide group (0.30 ± 0.15 vs. 0.39 ± 0.15; P= 0.003). In a regression analysis, there was a significant correlation between the infarct size and the AAR for both treatment groups and an analysis of covariance showed that datapoints in the exenatide group lay significantly lower than for the placebo group (P= 0.011). There was a trend towards smaller absolute infarct size in the exenatide group (13 ± 9 vs. 17 ± 14 g; P= 0.11). No difference was observed in left ventricular function or 30-day clinical events. No adverse effects of exenatide were observed. CONCLUSION In patients with STEMI undergoing pPCI, administration of exenatide at the time of reperfusion increases myocardial salvage.

Cardioprotective effects of ischemic postconditioning in patients treated with primary percutaneous coronary intervention, evaluated by magnetic resonance.

Background—Postconditioning has been suggested to reduce myocardial damage during primary percutaneous coronary intervention (PPCI) in patients with ST-segment–elevation myocardial infarction. However, because clinical experience is limited, we examined the cardioprotective effects of postconditioning, using cardiac MRI in patients treated with PPCI. Methods and Results—One hundred eighteen patients with ST-segment–elevation myocardial infarction referred for PPCI were randomly assigned to have either conventional PPCI or PPCI with postconditioning. Postconditioning was performed immediately after obtained reperfusion with 4 balloon occlusions, each lasting 30 seconds, followed by 30 seconds of reperfusion. The primary end point was myocardial salvage after 3 months as judged by delayed enhancement cardiac MRI. We found a 19% relative reduction of infarct size in the postconditioning group (51±16% of total area at risk versus 63±17%, P<0.01), corresponding to a 31% increase in salvage ratio. The number of patients developing heart failure was significantly fewer in the postconditioning group (27% versus 46%, P=0.048). No significant evidence of interaction between the impact of postconditioning and the location of the culprit lesion or size of the myocardium at risk was detected (P=0.21 and P=0.71). Conclusions—Mechanical postconditioning reduces infarct size in patients with ST-segment–elevation myocardial infarction treated with PPCI. The impact of mechanical postconditioning seems to be independent of the size of myocardium at risk. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00507156.

Exenatide Reduces Final Infarct Size in Patients With ST-Segment–Elevation Myocardial Infarction and Short-Duration of Ischemia

Background— Exenatide has been demonstrated to be cardioprotective as an adjunct to primary percutaneous coronary intervention in patients with ST-segment–elevation myocardial infarction (STEMI). The aim of the post hoc analysis study was to evaluate the effect of exenatide in relation to system delay, defined as time from first medical contact to first balloon. Methods and Results— Patients with STEMI and Thrombolysis In Myocardial Infarction flow 0/1 were randomly assigned to intravenous exenatide or placebo continuous infusion. Study treatment was commenced 15 minutes before intervention and maintained for 6 hours after the procedure. The patients were stratified according to median system delay (132 minutes). Final infarct size and myocardial area at risk were measured by cardiovascular magnetic resonance. Among patients with a system delay ⩽132 minutes (n=74), treatment with exenatide resulted in a smaller infarct size (9 grams [interquartile range (IQR), 4–13] versus 13 grams [IQR, 8–24], P=0.008, corresponding to 8% [IQR, 4–12] versus 11% [IQR, 7–17] of the left ventricle, P=0.015). In a regression analysis adjusting for myocardial area at risk the data points of the exenatide group lay significantly lower than for the placebo group (P=0.006). In the patients with system delay >132 minutes (n=74) no difference was observed in infarct size expressed as grams (P=0.49) or percentage (P=0.46). There was significant interaction between system delay (less than or equal to median versus greater than median) and treatment allocation in terms of infarct size (P=0.018). Conclusions— In this post hoc analysis, exenatide treatment was associated with a 30% decrease in final infarct size in patients with short system delay, whereas no cardioprotective effect in patients with long system delay was seen. However, this finding must be confirmed in larger studies. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00835848.

Combination therapy with bosentan and sildenafil in Eisenmenger syndrome: a randomized, placebo-controlled, double-blinded trial

AIMS To evaluate the efficacy of combining the dual endothelin receptor antagonist, bosentan, and the phosfodiesterase-5-inhibitor, sildenafil, in patients with Eisenmenger syndrome. METHODS AND RESULTS The study was a randomized, placebo-controlled, double-blinded, cross-over design. Patients with Eisenmenger syndrome (n = 21) were treated open label with bosentan for 9 months. After 3 months, sildenafil/placebo was added for 3 months, and a cross-over was performed for the last 3 months. At baseline and after 3, 6, and 9 months, patients were examined with 6 min walk test, oxygen saturations, N-terminal pro-brain natriuretic peptide, New York Heart Association (NYHA) classification, cardiac catheterization, and magnetic resonance imaging. The primary endpoint was changed in 6 min walk distance (MWD). Bosentan improved the 6 MWD (377 vs. 414 m, P = 0.001), pulmonary vascular resistance (PVR) (28 vs. 22 wood, P = 0.01), and pulmonary blood flow (2.6 vs. 3.5 L/min, P = 0.01). Adding sildenafil to bosentan did not improve the 6 MWD significantly (21 vs. 8 m, P = 0.48), but increased saturation at rest (2.9 vs. -1.8%, P < 0.01). CONCLUSION In Eisenmenger syndrome, treatment with bosentan significantly improved walking distance, pulmonary blood flow, and PVR. Adding sildenafil to bosentan did not significantly improve walking distance but did increase saturation at rest. http://www.ClinicalTrial.gov: NCT00303004.

Final infarct size measured by cardiovascular magnetic resonance in patients with ST elevation myocardial infarction predicts long-term clinical outcome: an observational study

AIMS Tailored heart failure treatment and risk assessment in patients following ST-segment elevation myocardial infarction (STEMI) is mainly based on the assessment of the left ventricular (LV) ejection fraction (EF). Assessment of the final infarct size in addition to the LVEF may improve the prognostic evaluation. To evaluate the prognostic importance of the final infarct size measured by cardiovascular magnetic resonance (CMR) in patients with STEMI. METHODS AND RESULTS In an observational study the final infarct size was measured by late gadolinium enhancement CMR 3 months after initial admission in 309 patients with STEMI. The clinical endpoint was a composite of all-cause mortality and admission for heart failure. During the follow-up period of median 807 days (IQR: 669-1117) 35 events (5 non-cardiac deaths, 3 cardiac deaths, and 27 admissions for heart failure) were recorded. Patients with a final infarct size ≥ median had significantly higher event rates than patients with a final infarct size <median (17 vs. 6%; Log rank P = 0.002). In a multivariable Cox regression analysis, including age, peak troponin T, LVEF, LV volume index, and heart rate, the final infarct size remained significantly associated with the occurrence of subsequent events (adjusted hazard ratio 1.13 per 1% increase (95% CI: 1.05-1.21; P = 0.001). The overall Wald χ(2) value of a model including known risk factors was 47.3, which increased to 57.9 when the final infarct size was added (P = 0.001 for the difference). CONCLUSION Assessment of the final infarct size by CMR 3 months after a STEMI provides strong independent prognostic information incremental to known risk factors including the LVEF, and may help to improve the risk stratification of STEMI patients.

Pregnancy with prosthetic heart valves — 30 years’ nationwide experience in Denmark

OBJECTIVE Pregnancy in women with prosthetic heart valves remains a risk factor for both mother and fetus, but unselected and unbiased outcome and complication data remain scarce. We analyzed nationwide outcome data from 1977 to 2007 for all pregnancies in women with prosthetic valves. METHODS Cardiac, obstetric, and neonatal data were obtained from obligatory databases and compared with general female population data. Questionnaires were used to corroborate important information. Outcome data were analyzed according to type of anticoagulation used. The data were compared between the two first and the last decades of the study period. In the last decade, patients were compared to an age-adjusted selected population of healthy, pregnant women. RESULTS Of 356 women between 15 and 40 years of age, 79 women had 155 pregnancies after valve replacement. Two women died during pregnancy, one from heart failure and one from post-partum bleeding. There were four thrombo-embolic episodes in the early study period in women with mitral prosthesis on unfractionated heparin. Important cardiac complications were otherwise almost absent. There were significantly more early miscarriages and terminations in patients compared with controls (last decade 34%, vs 20% (p=0.0036) and 26% vs 13% (p=0.000019)). Post-partum bleeding was more common in the patient group (p=0.0021). Two late fetal losses (one from intracerebral bleeding) were seen. The remaining pregnancies resulted in 60 live births. Cesarean section was the predominant method of delivery in patients as opposed to controls (55% vs 16%, p=0.000000000097). Premature births were more frequent in patients (49% vs 5.5%, p=0.00000000039) as were congenital malformations (14% vs 5.7%, p=0.044). Two of the six malformations were warfarin embryopathy (8% of all first-trimester warfarin exposures), both seen in high-risk patients on high warfarin dosing. Small for gestational age did not differ significantly from the general population (9.3% vs 6.0%, p=0.39). CONCLUSION Data acquired over 30 years confirm that women with prosthetic heart valves, especially aortic prostheses for congenital lesions, generally tolerate pregnancy well, although cardiac mortality, mortality related to anticoagulation and thrombo-embolic risks are raised. Our data provide further documentation on the significance and importance of the risks associated with predominantly warfarin-based treatment regimens, which still remains optional for a number of patients. Finally, the data also serve as a comparison for recently published series based on low-molecular-weight heparin (LMWH) regimens.

Left atrial volume and function in patients following ST elevation myocardial infarction and the association with clinical outcome: a cardiovascular magnetic resonance study

AIMS The left atrium (LA) transfers blood to the left ventricle in a complex manner. LA function is characterized by passive emptying (LA passive fraction), active emptying (LA ejection fraction), and total emptying (LA fractional change). Despite this complexity, the clinical relevance of the LA is based almost exclusively on LA maximal volume (LAmax), which may not glean the full prognostic potential. Cardiovascular magnetic resonance (CMR) is considered the most accurate method for studying LA function and size. The aim of the present study was to evaluate the prognostic importance of LA function in patients following ST elevation myocardial infarction (STEMI). METHODS AND RESULTS In 199 patients, a CMR scan was performed within 1-3 days after STEMI to measure LAmax and minimal volume (LAmin) and LA function. The incidence of death, re-infarction, stroke, and admission for heart failure [major adverse cardiac event (MACE)] were registered during the follow-up period [2.3 years (inter-quartile range: 2.0-2.5)]. A total of 40 patients (20%) met the clinical endpoint of MACE during follow-up. In a Cox regression analysis adjusting for known risk factors, LA fractional change remained independently associated with MACE [adjusted hazard ratio: 0.66 (95% confidence interval: 0.46-0.95)]. LAmax, LAmin, or LA passive fraction was not independently associated with MACE. Furthermore, LA fractional change provided incremental prognostic value to LAmax and other known predictors (Wald χ(2) 31.0 vs. 39.9, P= 0.016). CONCLUSION In STEMI patients, impaired LA fractional change is independently associated with outcome and provide incremental prognostic information to established predictors including LAmax.

Impact of system delay on infarct size, myocardial salvage index, and left ventricular function in patients with ST-segment elevation myocardial infarction.

BACKGROUND The association between reperfusion delay and myocardial damage has previously been assessed by evaluation of the duration from symptom onset to invasive treatment, but results have been conflicting. System delay defined as the duration from first medical contact to first balloon dilatation is less prone to bias and is also modifiable. The purpose was to evaluate the impact of system delay on myocardial salvage index (MSI) and infarct size in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention (PCI). METHODS In patients with ST-elevation myocardial infarction, MSI and final infarct size were assessed using cardiovascular magnetic resonance. Myocardial area at risk was measured within 1 to 7 days, and final infarct size was measured 90 ± 21 days after intervention. Patients were grouped according to system delay (0 to 120, 121 to 180, and >180 minutes). RESULTS In 219 patients, shorter system delay was associated with a smaller infarct size (8% [interquartile range 4-12%], 10% [6-16%], and 13% [8-17%]; P < .001) and larger MSI (0.77 [interquartile range 0.66-0.86], 0.72 [0.59-0.80], and 0.68 [0.64-0.72]; P = .005) for a system delay of up to 120, 121 to 180, and >180 minutes, respectively. A short system delay as a continuous variable independently predicted a smaller infarct size (r = 0.30, P < .001) and larger MSI (r = -0.25, P < .001) in multivariable linear regression analyses. Finally, shorter system delay (0-120 minutes) was associated with improved function (P = .019) and volumes of left ventricle (P = .022). CONCLUSIONS A shorter system delay resulted in smaller infarct size, larger MSI, and improved LV function in patients treated with primary PCI. Thus, this study confirms that minimizing system delay is crucial for primary PCI-related benefits.

Prognostic importance of complete atrioventricular block complicating acute myocardial infarction

Third-degree atrioventricular block after acute myocardial infarction is considered to have prognostic importance. However, its importance in conjunction with thrombolytic therapy and its relation to left ventricular function remains uncertain. This report also outlines an important distinction between atrioventricular block in the setting of anterior and inferior wall acute myocardial infarction, with profound clinical and prognostic implications.