Inspiratory muscle dysfunction and restrictive lung function impairment in congenital heart disease: Association with immune inflammatory response and exercise intolerance.

BACKGROUND: In adult patients with congenital heart disease (ACHD), both underlying disease and lung restriction contribute to exercise intolerance. In ACHD the yet incompletely understood mechanism underlying restricted ventilation may be inspiratory muscle weakness. Therefore, this study comprehensively evaluated inspiratory muscle function in ACHD and associations with systemic inflammation and the clinical severity of exercise intolerance. METHODS: 30 ACHD patients (21 men, 35 ± 12 years) and 30 healthy controls matched for age, gender and body mass index underwent spirometry, measurement of mouth occlusion pressures, and diaphragm ultrasound. Six-minute walking distance (6MWD) and New York Heart Association functional class were used to quantify exercise intolerance. Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels were measured using enzyme-linked immunosorbent assays. RESULTS: ACHD patients showed lower forced vital capacity (FVC), and maximum inspiratory (PImax) and expiratory (PEmax) pressures compared with controls (all p < 0.05). On ultrasound, ACHD patients showed a lower diaphragm thickening ratio (2.3 ± 0.5 vs. 2.8 ± 0.9, p < 0.01) and lower diaphragm excursion velocity during a voluntary sniff maneuver (5.7 ± 2.2 vs. 7.6 ± 2.0 cm/s, p < 0.01). Respiratory parameters, such as FVC (r = 0.53; p < 0.01) and PImax (r = 0.43; p = 0.02), correlated with 6MWD. Furthermore, amino terminal pro B-type natriuretic peptide levels were inversely correlated with FVC (r = -0.54; p < 0.01). Circulating pro-inflammatory cytokines were markedly increased, and IL-6 was correlated with 6MWD, dyspnea, and biomarkers of heart, lung and inspiratory muscle function (all p < 0.05). CONCLUSIONS: Our findings show that diaphragm dysfunction is present in ACHD and relates to restrictive ventilation disorder and exercise intolerance, possibly mediated by increased IL-6 levels.

Effect of Atrial Fibrillation and Mitral Valve Gradients on Response to Percutaneous Mitral Valve Repair With the MitraClip System.

Both pre-existing atrial fibrillation (AF) and mitral valve pressure gradients (MVPG) created by MitraClip implantation have demonstrated predictive power for unfavorable outcomes. Therefore, we aimed to assess the impact of MVPG following MitraClip on outcomes in patients with and without AF. A total of 200 patients who underwent MitraClip implantation in our institution were enrolled. Echocardiography was obtained before and after the procedure. The primary endpoint of the study was all-cause mortality 1-year after MitraClip implantation. Secondary end points were clinical improvements in NYHA functional class and reduction in MR severity after MitraClip implantation. Two hundred patients (74 ± 10 years, left ventricular ejection fraction 41% ± 14%, logistic EuroSCORE I 21 ± 15) were enrolled into the final analysis. One hundred twelve patients (56%) had pre-existing AF. One-year all-cause mortality was 17% without any differences between patients with or without pre-existing AF. Comparing postprocedural MVPG of surviving and deceased patients, deceased patients with pre-existing AF exhibited significantly elevated postprocedural MVPG compared with surviving patients without AF (4.8 ± 2.1 mm Hg vs 3.6 ± 1.8 mm Hg; p = 0.010). ROC analysis and Kaplan-Meier survival curves identified significantly reduced survival in AF patients with postprocedural MVPG above 4.0 mm Hg (p = 0.011). After MitraClip, a MVPG above 4.0 mm Hg in patients with pre-existing AF was a significant outcome predictor in univariate and multivariate analysis. In conclusion, we identified a high-risk cohort characterized by postprocedural MVPG above 4.0 mm Hg and pre-existing AF predicting poor long-term outcome.

Effect of Acute Kidney Injury After Percutaneous Mitral Valve Repair on Outcome.

Limited data exist on the occurrence of acute kidney injury (AKI) associated with percutaneous mitral valve repair (PMVR). The objectives of the present study were (1) to assess the prevalence of AKI after MitraClip (Abbott Vascular, Santa Clara, California) implantation, (2) to analyze the predictive factors of AKI, and (3) to evaluate the prognostic value of AKI after PMVR with a view to optimizing the management of high-risk patients. A total of 206 patients (serum creatinine [SCr] 1.3 ± 0.6 mg/dl, estimated glomerular filtration rate 55 ± 24 ml/min) who underwent PMVR were included. AKI was defined as an increase in SCr by ≥0.3 mg/dl within 48 hours or an increase in SCr by ≥1.5 times baseline. AKI was assessed during the first 5 days after MitraClip implantation. The incidence of AKI after MitraClip was 18% and none of the patients required dialysis. Age, logistic EuroSCORE, baseline renal function, N-terminal pro-B-type natriuretic peptide levels, serum glycated hemoglobin A1c, serum C-reactive protein, diuretic usage, and elevated right atrial pressure were the risk factors of AKI. Incidence of AKI was associated with poor outcome. Short-term mortality was increased (30-day mortality rate AKI vs no AKI: 18% vs 1%; p <0.001). Likewise, Kaplan-Meier analysis and log-rank test confirmed reduced long-term survival of patients with AKI (1-year all-cause mortality of patients with AKI vs patients with no AKI: 34% vs 13 %; p <0.001). In conclusion, every fifth patient experienced AKI after MitraClip implantation, which was associated with increased short-term mortality and a more than threefold increase in the risk of death 1 year after PMVR.

Abnormal T2 mapping cardiovascular magnetic resonance correlates with adverse clinical outcome in patients with suspected acute myocarditis.

BACKGROUND: While most patients recover from suspected acute myocarditis (sAMC) some develop progressive disease with 5-year mortality up to 20%. Recently, parametric Cardiovascular Magnetic Resonance (CMR) approaches, quantifying native T1 and T2 relaxation time, have demonstrated the ability to increase diagnostic accuracy. However, prognostic implications of T2 values in this cohort are unknown. The purpose of the study was to investigate the prognostic relevance of elevated CMR T2 values in patients with sAMC. METHODS AND RESULTS: We carried out a prospective study in 46 patients with sAMC defined by current ESC recommendations. A combined endpoint was defined by the occurrence of at least one major adverse cardiac event (MACE) and hospitalisation for heart failure. Event rate was 24% (n = 11) for 1-year-MACE and hospitalisation. A follow-up after 11 ± 7 months was performed in 98% of the patients. Global T2 values were significantly increased at acute stage of disease compared to controls and decreased over time. During acute disease, elevated global T2 time (odds ratio 6.3, p < 0.02) as well as myocardial fraction with T2 time >80 ms (odds ratio 4.9, p < 0.04) predicted occurrence of the combined endpoint. Patients with clinical recovery revealed significantly decreased T2 relaxation times at follow-up examinations; however, T2 values were still elevated compared to healthy controls. CONCLUSION: Assessment of myocardial T2 relaxation times at initial presentation facilitates CMR-based risk stratification in patients with acute myocarditis. T2 Mapping may emerge as a new tool to monitor inflammatory myocardial injuries during the course of disease.