| Non-ischemic dilated cardiomyopathy (NIDCM) is one of the most common underlying cause of new-onset heart failure (HF), and accounts for a significant proportion among patients on heart transplant waiting list worldwide. It is generally characterized by left or biventricular dilatation in addition to systolic dysfunction in the absence of abnormal loading conditions (hypertension, valve disease) or coronary artery disease sufficient to cause global systolic impairment. However, two kinds of coronary lesion often ignored advertently.Non-obstructive coronary stenosis has also been pathologically identified in the hearts of patients diagnosed with NIDCM who have to undergo heart transplantation because of decompenstated HF, which means patients with NIDCM can present or develop coronary stenosis concomitant to their primary disease. Whereas, clinical data of concomitant coronary in patients with NIDCM is still largely unknown. Furthermore, whether combined coronary stenosis play a role in the evolution of ventricular dysfunction and influence heart failure progression in the patients with NIDCM is still far from being fully elucidated. More investigations are still needed to improve our understanding of this issue.In addition, myocardial bridging, an inborn coronary abnormality, is also thought to be a benign anatomic variation. Patients with myocardial bridging are often asymptomatic, but this anomaly may be associated with exertional angina, acute coronary syndromes, cardiac arrhythmias, syncope, or even sudden cardiac death. Clinical characteristics, morbidity and prognostic value of concomitant myocardial bridging in patients with NIDCM are still incompletely understood.Pathological coronary artery anatomy (PCA) is always considered as the gold standard for diagnosis of coronary artery disease (CAD) in addition to conventional coronary angiography (CCA), postoperative PCA examination in hearts excised at transplantation can help us to further understand the detail characteristics and prognostic value of combined coronary stenosis or myocardial bridging in NIDCM patients. This study retrospectively investigate the pathology of coronary trees in NIDCM patients who underwent heart transplantation at Fuwai hospital, through comprehensive analyses of the clinical significance of combined coronary stenosis or myocardial bridging in these patients, we hope to deepen the cognition of these disease and then guide the clinical decision making in the future.Part 1:Clinical significance of mild coronary stenosis in patients with non-ischemic dilated cardiomyopathy:insights from pathological coronary artery anatomyObjective:The present study was designed to investigate the clinical characteristics and identify predictors of concomitant mild coronary stenosis in patients with NIDCM, then evaluate whether mild coronary stenosis plays a role in the evolution of left ventricular dysfunction.Methods:From June 2004 to July 2014,445 consecutive patients who underwent heart transplantation for NIDCM at Fuwai hospital were considered for the study. Explanted heart excised at transplantation underwent systematic pathological investigation. All of the clinical and pathological data were carefully collected and recorded onto computerized database. After analysis the incidence of concomitant mild coronary stenosis, univariable and multivariable logistic regression were performed using coronary artery status as dependent variable to determine the predictors of this combined disease. Then, the cohort will be grouping based on the presence of coronary stenosis and 1:1 matched by propensity score to address the prognostic value of concomitant mild coronary stenosis. Finally, we performed subgroup analyses for different ages, lesion locations and the number of vessels.Results:Of the 445 patients,243 were diagnosed with NIDCM. Of these latter,220 met the inclusion criteria and entered in the study. Mild coronary stenosis were pathologically found in 33 patients(15%). Multivariate logistic analysis showed that age (OR=1.06,95%CI:1.02-1.12,p).005) and dyslipidemia (OR=4.06, 95%CI:1.59-10.35, p=0.003) were significant independent predictors of mild coronary stenosis. After propensity score matching, we found that the mean diagnose-heart transplantation interval (years) in the NICDM patients combined with mild coronary stenosis was remarkably shorter than the patients without. This trend is more apparent in patients aged> 50. However, coronary lesion locations and the number of vessels did not influence the results, and the presence of concomitant conronary stenosis appears not to be associated with severe pathological changes or adverse prognosis in hospital.Conclusions:Concomitant mild coronary stenosis can be developed in approximately 15% patients with NIDCM, with age and dyslipidemia were independent predictors. The presence of this combined disease may accelerate heart failure progression in the NIDCM patients. Part 2:Impact of concomitant myocardial bridging in patients with non-ischemic dilated cardiomyopathy: clinical and metabolomic analysisObjective:To determine the frequency, anatomic features and clinical implication of myocardial bridging in NIDCM. Metabonomics analysis were aslo performed to further investigate the biochemical effects of myocardial bridging on NIDCM patientsMethods:We performed a large cohort study in 292 consecutive patients with end-stage heart failure who had undergone heart transplantation in Fuwai Hospital from June 2004 to December 2011. The medical records were retrospectively reviewed and hearts collected after the transplantation were histopathologically and anatomically examined. Then, the myocardial bridging was studied with respect to their length, depth and distance from the coronary osmium of submersion within LV myocardium, and the myocardium in distal regions were obtained and to found whether myocardium have ischemia or not. After 1:1 propensity score matching, the prognostic value of concomitant myocardial bridging was evaluated between these two groups. Finally, High Performance Liquid Chromatography/Mass Spectrometry (HPLC/MS) based metabonomics analysis combined with pattern recognition techniques were performed to detect the endogenous metabolites present in the heart tissues of the Normal controls, NIDCM patients and NIDCM patients with myocardial bridging.Results:162 NIDCM patients were enrolled, and 31(19.14%) of them were pathologically found to have Myocardial bridging. Myocardial bridging is generally confined to the left anterior descending artery, with mean length of the compressed coronary segment were 25.08±11.17, depth was 3.25±2.06. Pathological taining found obvious ischemia, sarcomere disorganization and vacuoles. Furthermore, the time interval from the diagnosis of NIDCM to heart transplantation was shorter in patients combined with myocardial bridging than these patients without. Metabolomics profiling in heart tissues by HPLC/MS reveals that a total of 47 endogenous metabolites in the myocardial bridging group were significantly difference from the normal control including low-molecular-mass metabolites, such as essential amino acids, acidic amino acids, branched-chain amino acids, aromatic amino acids et al.22 endogenous metabolites were significantly difference from the DCM group, a number of glycolysis and tricarboxylic acid-cycle (TCA cycle) related metabolites and intermediates were detected in the heart tissues. Multivariate statistical analysis showed clear separation of the myocardial bridge group and control group suggested that severe metabolic disturbance happened in DCM patients with myocardial bridge.Conclusions:Myocardial bridging can be detected in about 1/5 of NIDCM patients and it’s a risk factor for heart failure progression due to myocardial bridging induced myocardial ischemia. |
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