Characterizing the inflammatory tissue response to acute myocardial infarction by clinical multimodality noninvasive imaging.

BACKGROUND: Myocardial infarction (MI) triggers a systemic inflammatory response which determines subsequent healing. Experimentally, cardiac positron emission tomography and magnetic resonance imaging have been used successfully to obtain mechanistic insights. We explored the translational potential in patients early after MI. METHODS AND RESULTS: Positron emission tomography/computed tomography and cardiac magnetic resonance were performed in 15 patients <7 days after first MI. Cardiac magnetic resonance showed regional transmural late gadolinium enhancement and edema exceeding the area of late gadolinium enhancement. Using F-18 deoxyglucose with heparin pretreatment, metabolic rate of glucose (MRGlc) was significantly increased in infarct versus remote myocardium (median, 2.0 versus 0.4 mg/min per 100 mL; P=0.0001). MRGlc in infarct correlated with remote myocardium (ρ=0.64; P=0.01), spleen (ρ=0.82; P=0.0002), and bone marrow(ρ=0.57; P=0.03), but not with muscle or liver. Regionally, F-18 deoxyglucose score was highest in segments with late gadolinium enhancement versus edema only and remote (median, 2.0 versus 1.8 versus 0.4; P<0.0001). Patients requiring repeat intervention during preliminary follow-up of 11±5 months tended to have higher early post-MI MRGlc. Five patients with chronic, stable MI served as controls. Opposite to acute MI, MRGlc was lower in infarct (median infarct/remote ratio, 0.6 versus 3.2 for acute MI; P=0.001), and there was no correlation with bone marrow or spleen MRGlc. CONCLUSIONS: Increased glucose utilization after heparin-induced suppression of myocyte uptake appears to mostly reflect inflammatory activity in damaged myocardium early after MI. Consistent with prior preclinical observations, and in contrast to chronic MI, this is associated with activity in spleen and bone marrow as sources of inflammatory cells. Positron emission tomography and cardiac magnetic resonance multimodality characterization of the acutely infarcted, inflamed myocardium may provide multiparametric end points for clinical studies aiming at support of infarct healing.

Declining cardiopulmonary exercise capacity is not associated with worsening systolic systemic ventricular dysfunction in adults with transposition of great arteries after atrial switch operation.

BACKGROUND/OBJECTIVE: Cardiopulmonary exercise capacity is often reduced in patients with transposition of the great arteries after atrial switch operation. Reduced exercise capacity may be caused by deterioration of systemic right ventricular function over time. This study analyzed serial changes in systemic right ventricular function and cardiopulmonary exercise capacity in young adults with transposition of the great arteries after atrial redirection surgery. METHODS: Twenty-one patients (37% female, mean age 23.2 ± 3.3, mean age at surgery 12.8 ± 14 years) with transposition of the great arteries after atrial switch operation were included in this study. Patients were followed up for a mean period of 39.6 ± 13.1 months. Exercise capacity expressed as peak VO2 max, systemic right ventricular function and subpulmonary left ventricular function assessed by cardiac magnetic resonance imaging and NT-proBNP levels were obtained at baseline and follow-up. Changes in peak VO2 max were correlated to changes in cardiac magnetic resonance imaging and NT-proBNP levels. RESULTS: Baseline peak VO2 max decreased significantly (28.31 ± 5.80 mL/kg/min vs. 25.17 ± 5.71 mL/kg/min, P = .005) on follow-up. Cardiac magnetic resonance imaging parameters of systemic right ventricular ejection fraction as well as subpulmonary left ventricular ejection fraction remained unchanged (44.68 ± 6.59% vs. 45.65 ± 9.60%, P = .54, 60.18 ± 6.29% vs. 61.52 ± 5.30%, P = .35). NT-proBNP levels did not increase (211.7 ± 85.7 ng/mL vs. 261.2 ± 182.2 ng/mL, P = .16). CONCLUSIONS: After atrial switch operation for transposition of the great arteries we observed a declining functional exercise capacity. This was not associated with worsening systemic right ventricular function, suggesting that other factors are contributing to the decline in physical exercise capacity.

Aerobic training in adults after atrial switch procedure for transposition of the great arteries improves exercise capacity without impairing systemic right ventricular function.

BACKGROUND: Exercise training safely and efficiently improves symptoms in patients with heart failure due to left ventricular dysfunction. However, studies in congenital heart disease with systemic right ventricle are scarce and results are controversial. In a randomised controlled study we investigated the effect of aerobic exercise training on exercise capacity and systemic right ventricular function in adults with d-transposition of the great arteries after atrial redirection surgery (28.2 ± 3.0 years after Mustard procedure). METHODS: 48 patients (31 male, age 29.3 ± 3.4 years) were randomly allocated to 24 weeks of structured exercise training or usual care. Primary endpoint was the change in maximum oxygen uptake (peak VO2). Secondary endpoints were systemic right ventricular diameters determined by cardiac magnetic resonance imaging (CMR). Data were analysed per intention to treat analysis. RESULTS: At baseline peak VO2 was 25.5 ± 4.7 ml/kg/min in control and 24.0 ± 5 ml/kg/min in the training group (p=0.3). Training significantly improved exercise capacity (treatment effect for peak VO2 3.8 ml/kg/min, 95% CI: 1.8 to 5.7; p=0.001), work load (p=0.002), maximum exercise time (p=0.002), and NYHA class (p=0.046). Systemic ventricular function and volumes determined by CMR remained unchanged. None of the patients developed signs of cardiac decompensation or arrhythmias while on exercise training. CONCLUSIONS: Aerobic exercise training did not detrimentally affect systemic right ventricular function, but significantly improved exercise capacity and heart failure symptoms. Aerobic exercise training can be recommended for patients following atrial redirection surgery to improve exercise capacity and to lessen or prevent heart failure symptoms. ( CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov #NCT00837603).

Circulating miR-423_5p fails as a biomarker for systemic ventricular function in adults after atrial repair for transposition of the great arteries.

BACKGROUND: Recently, the microRNA miR-423_5p was identified as a biomarker for left ventricular heart failure. Its role in patients with a systemic right ventricle and reduced ejection fraction after atrial repair for transposition of the great arteries has not been evaluated. METHODS: In 41 patients and 10 age- and sex-matched healthy controls circulating miR-423_5p concentration was measured and correlated to clinical parameters, cardiac functional parameters assessed by magnetic resonance imaging, and cardiopulmonary exercise testing. RESULTS: Levels of circulating miR-423_5p showed no difference between patients and controls. Further, there was no correlation between miR-423_5p and parameters of cardiopulmonary exercise testing or imaging findings. CONCLUSIONS: In patients with a systemic right ventricle and reduced ejection fraction miR-423_5p levels are not elevated. Therefore, circulating miR-423_5p is not a useful biomarker for heart failure in this patient group.

Pulmonary valve replacement in chronic pulmonary regurgitation in adults with congenital heart disease: impact of preoperative QRS-duration and NT-proBNP levels on postoperative right ventricular function.

BACKGROUND: Chronic severe pulmonary regurgitation (PR) causes progressive right ventricular (RV) dysfunction and heart failure. Parameters defining the optimal time point for surgery of chronic PR are lacking. The present study prospectively evaluated the impact of preoperative clinical parameters, cardiorespiratory function, QRS duration and NT-proBNP levels on post operative RV function and volumes assessed by cardiac magnetic resonance imaging (CMR) in patients with chronic severe PR undergoing pulmonary valve replacement. METHODS AND RESULTS: CMR was performed pre- and 6 months postoperatively in 27 patients (23.6 ± 2.9 years, 15 women) with severe PR. Postoperatively, RV endsystolic (RVESVI) and enddiastolic volume indices (RVEDVI) decreased significantly (RVESVI pre 78.2 ± 20.4 ml/m² BSA vs. RVESVI post 52.2 ± 16.8 ml/m²BSA, p<0.001; RVEDVI pre 150.7 ± 27.7 ml/m²BSA vs. RVEDVI post 105.7 ± 26.7 ml/m²BSA; p<0,001). With increasing preoperative QRS-duration, postoperative RVEF decreased significantly (r=-0.57; p<0.005). Preoperative QRS-duration smaller than the median (156 ms) predicted an improved RVEF compared to QRS-duration≥ 156 ms (54.9% vs 46.8%, p<0.05). Multivariate analysis identified preoperative QRS duration as an independent predictor of postoperative RVEF (p<0.005). NT-proBNP levels correlated with changes in RVEDI (r=0.58 p<0,005) and RVESVI (r=0.63; p<0,0001). Multivariate analysis identified NT-proBNP levels prior to PVR as an independent predictor of volume changes (p<0.05). CONCLUSION: Valve replacement in severe pulmonary regurgitation causes significant reduction of RV volumes. Both, preoperative NT-proBNP level elevation and QRS prolongation indicate patients with poorer outcome regarding RV function and volumes.

Left ventricular assist improves autonomic imbalance in patients with persistent myocardial dysfunction.

BACKGROUND: Left ventricular assist devices (LVAD) are an effective therapeutic option for end-stage heart failure (HF). Reduced heart rate variability (HRV) as a result of autonomic derangement is evident in chronic heart failure and several studies have established the independent prognostic value of HRV in chronic heart failure. OBJECTIVE: In the present study we investigated whether autonomic function is restored in patients after LVAD implantation with persistent, severely depressed left ventricular function. METHODS: Ambulatory Holter ECG recordings were collected in heart failure patients with an LVAD (n=8) und age-matched heart failure patients without an LVAD (n=7) both on optimal medical therapy. Cardiac dimensions and function were assessed by echocardiography or angiography. RESULTS: Analysis for heart rate variability revealed reduced SDNN (67±4 ms), SDANN (56±4 ms) and triangular index (18±1) in heart failure patients on optimal medical therapy. However patients with LVAD demonstrated a restoration in heart rate variability with normal SDNN (108±9 ms), SDANN (103±8 ms) and triangular index (29±2). Compared to patients without LVAD this difference was statistically significant (p<0.01). CONCLUSIONS: In end-stage heart failure patients autonomic imbalance indicated by severely reduced heart rate variability is restored after LVAD implantation with unloading of the failing heart.

Pregnancy in a Marfan patient with pre-existing aortic dissection.

In women with Marfan syndrome pregnancy increases the risk of aortic dissection. There are a number of articles reporting the outcome of acute aortic dissection during pregnancy in this patient group. In contrast, only scarce information is available concerning pregnancy in patients with pre-existing chronic aortic dissection. We report the case of a pregnant Marfan syndrome patient with pre-existing chronic aortic dissection that showed a favourable maternal and fetal outcome.