Synthesis and dopaminergic neuroprotective activity of the proposed structure of bassiamide A, a caffeamide alkaloid derived from Bassia indica Wight.

Herein, we describe the synthesis of the proposed structure of the caffeamide alkaloid bassiamide A. The amide moiety of bassiamide A was readily formed via an amide coupling reaction between caffeic acid and the known N-(3-aminopropyl)-3-methylbutanamide. However, the spectral data of the synthesized bassiamide A did not agree with that of a previous study. The structure of the synthesized bassiamide A was confirmed using combined two-dimensional NMR analysis. Extended analyses of the bioactivity of the synthesized bassiamide A revealed its efficacy in protecting dopaminergic neurons from MPP+-induced neurotoxicity in C. elegans. Additionally, treatment with bassiamide A notably ameliorated the impaired food-sensing ability and locomotion of C. elegans, suggesting a protective effect on the functionality of dopaminergic neurons.

Synthesis of a natural quinoline alkaloid isolated from the deep-sea-derived fungus and its potential as a therapeutic for Parkinson's disease.

2-(Quinoline-8-carboxamido)benzoic acid (2-QBA; 1) is a natural quinoline alkaloid isolated from the deep-sea-derived fungus Aspergillus sp. SCSIO06786. Alkaloid 1 was synthesized by an amidation reaction of 8-quinolinecaroxylic acid with methyl anthranilate, followed by hydrolysis. The neuroprotective properties of 1 were evaluated using a Caenorhabditis elegans Parkinson's disease model, which revealed that 1 significantly ameliorated 1-methyl-4-phenylpyridinium (MPP+)-induced dopaminergic neurodegeneration in a dose-dependent manner. MPP+-induced behavioral defects in worms, including impaired locomotion and basal slowing ability, were restored by treatment with 1. We further demonstrated that treatment with 1 modulates the formation of neurotoxic α-synuclein oligomers by suppressing α-synuclein expressions and enhancing proteasome activity. These results suggest that 1 is a promising therapeutic candidate for the treatment of Parkinson's disease.

Synthesis of Evodileptin B, a Natural Anthranilate Derivative Isolated from Evodia lepta, and Evaluation of Its Therapeutic Potential against Parkinson's Disease.

Evodileptin B (1) is a natural anthranilate derivative isolated from the ethanol extract of the aerial parts of Evodia lepta (Spreng.) Merr., a traditional medicinal plant of the family Rutaceae. We readily synthesized 1 via the amidation of phloretic with methyl anthranilate and evaluate its neuroprotective activity using a C. elegans Parkinson's disease (PD) model. The results showed that evodilpetin B ameliorated MPP+ -induced dopaminergic (DA) neurodegeneration in a dose-dependent manner. Evodileptin B treatment also significantly improved the DA neurotransmission-related behavioral defects such as reduced locomotory and food-sensing ability of worms under MPP+ exposure conditions, suggesting its potential application for the functional restoration of DA neurons. In addition, we found that 1 has an ability to regulate aggregation of α-synuclein by increasing proteasome activity in the human α-synuclein-expressing mutant worms. These results demonstrate that evodileptin B has strong neuroprotective properties and may be useful in the treatment of PD.

Synthesis of Proposed Structure of Aaptoline A, a Marine Sponge-Derived 7,8-Dihydroxyquinoline, and Its Neuroprotective Properties in C. elegans.

A concise and efficient synthesis of the proposed structure of aaptoline A, a 7,8-dihydroxyquinoline derived from a marine sponge, was accomplished in seven steps with a 52% overall yield. A key feature of the synthesis is the high-yielding Ag(I)-catalyzed cycloisomerization of the N-propargylaniline precursor to afford the quinoline carboxylate skeleton from acid-labile methyl aminobenzoate. However, the spectral data of the synthesized aaptoline A were not consistent with those of previous studies. The structure of the synthesized aaptoline A was confirmed by combined 2D NMR analysis. Additional studies on the bioactivity of the synthesized aaptoline A revealed that it has the ability to protect dopaminergic neurons against MPP+-induced neurotoxicity in C. elegans. In addition, impaired food-sensing ability and travel distance capability in C. elegans were significantly ameliorated by aaptoline A treatment, suggesting that aaptoline A can protect dopaminergic neurons both morphologically and functionally.

Clinical features differentiating Takotsubo cardiomyopathy in the peripartum period from peripartum cardiomyopathy.

There are some similarities in clinical features between Takotsubo cardiomyopathy during the peripartum period (PTCM) and peripartum cardiomyopathy (PPCM). Both conditions present as acute heart failure and decreased left ventricular (LV) ejection fraction in the peripartum period in previously heart-healthy women. The present study aimed to evaluate the differences in clinical features and outcomes between PTCM and PPCM. Between January 2004 and December 2016, 37 consecutive patients who demonstrated LV dysfunction during the peripartum period without previous heart disease were recruited retrospectively. The clinical, laboratory, and echocardiographic data of these patients were comprehensively reviewed. Twenty-one (57%) and 16 (43%) patients were classified into PPCM and PTCM groups, respectively, based on echocardiographic findings. The initial LV ejection fraction did not differ significantly between the 2 groups. However, all patients with PTCM showed complete recovery of LV ejection fraction at the 1-month follow-up. However, among 20 patients with PPCM who underwent 1-month echocardiography, only 6 (30%) showed complete recovery of LV ejection fraction at the 1-month follow-up. At the 12-month follow-up, only 10 patients showed complete recovery of LV ejection fraction. The incidence of PTCM was much higher than expected. Although LV dysfunction was similar at the initial diagnosis, the prognosis of LV recovery was more favorable in PTCM than in PPCM. Therefore, physicians should differentiate these two diseases entities, although they have several similarities in acute LV dysfunction.

Post-operative left atrial volume index is a predictor of the occurrence of permanent atrial fibrillation after mitral valve surgery in patients who undergo mitral valve surgery.

BACKGROUND: Atrial fibrillation (AF) can occur even after the correction of mitral valve (MV) pathology in patients who have pre-operative sinus rhythm and undergo MV surgery. However, the factors associated with the occurrence of AF after MV surgery are still unclear. The aim of this retrospective study was to investigate the factors determining the occurrence of permanent AF after MV surgery in patients with preoperative sinus rhythm who underwent MV surgery. METHODS: Four hundred and forty-two patients (mean age 46 ± 12, 190 men) who underwent MV surgery and sinus rhythm were investigated retrospectively. Transthoracic echocardiography was performed before and after MV surgery at the time of dismissal. RESULTS: Permanent post-operative AF occurred in 81 (18%) patients even after successful MV surgery and preoperative sinus rhythm. It was more common in rheumatic etiology, a presence of mitral stenosis, lower pre- and post-operative left ventricular ejection fraction, higher post-operative mean diastolic pressure gradient across mitral prosthesis, larger post-operative left atrial volume index (LAVI) and lesser degrees of reduction in LAVI after surgery. In multiple regression analysis, post-operative LAVI was found to be an independent predictor for occurrence of AF. Post-operative LAVI > 39 ml/m2 was the cut-off value for best prediction of new onset permanent AF (sensitivity: 79%, AUC: 0.762, SE: 0.051, p < 0.001). CONCLUSION: New-onset permanent post-operative AF is not uncommon, even after successful MV surgery despite pre-operative sinus rhythm. Larger post-operative LAVI was an independent predictor for the occurrence of AF.

Incremental predictive value of carotid arterial strain in patients with stroke.

Although increased carotid intima-media thickness (IMT) is a well-known risk factor for stroke, carotid IMT alone is not sufficient for risk stratification. The assessment of arterial properties using velocity vector imaging (VVI) represents a new method for quantifying structural changes. We sought to investigate the characteristics and the clinical value of carotid arterial mechanics using VVI in patients with stroke. Fifty male patients (55 ± 5 years) with stroke, 30 healthy age-matched volunteers (54 ± 8 years), and 30 healthy young male volunteers (29 ± 5 years) were evaluated. The peak circumferential strain, strain rate, and the standard deviation of the time to peak strain and strain rate, representing the synchronicity of the arterial expansion, were analyzed using VVI of the left common carotid artery. The circumferential strain and strain rate significantly decreased with age, and patients with stroke showed the lowest degree of strain and strain rate compared with healthy age-matched volunteers. In addition, patients with stroke showed decreased strain and strain rate even in participants with a normal carotid IMT (< 0.8 mm). Although carotid IMT did not improve the incremental predictive value of stroke over that of multiple clinical risk factors (diabetes mellitus, hypertension, coronary artery disease, smoking), adding carotid arterial strain and strain rate provided an incremental predictive value over both multiple risk factors and carotid IMT for stroke. Along with assessment of conventional risk factors, VVI analysis could provide improved risk stratification for stroke.

Association of elevated blood pressure during exercise with cerebral white matter lesions.

OBJECTIVES: Cerebral white matter lesions (WMLs) are regarded to be subclinical ischemic changes of the cerebral parenchyma. Many previous studies have shown that baseline blood pressure (BP) is one of the most important factors for WMLs, but the relation between exercise BP and WMLs has not been fully evaluated. So, we sought to investigate the relationships between cerebral WMLs and peak exercise BP. METHODS: Brain magnetic resonance imaging scan and treadmill testing were performed simultaneously in 130 consecutive subjects without history of stroke or transient ischemic stroke. RESULTS: Among 130 subjects, 42 individuals (32%) presented WMLs. Individuals with WMLs were older than those without WMLs, and baseline systolic BP and pulse pressure were higher in subjects with WMLs. During treadmill test, peak exercise systolic BP was more significantly elevated in subjects with WMLs. In multivariable logistic regression analysis, elevated baseline systolic BP, not peak exercise systolic BP, was associated with the presence of WMLs, independently of age. However, in multivariable logistic regression analysis of 88 normotensive subjects, elevated peak systolic BP during exercise was the only determinant for the presence of WMLs. CONCLUSIONS: Elevated peak systolic BP during exercise is significantly related with WMLs, subclinical small vessel disease of brain, especially in normotensive subjects.

Serial measurements of neutrophil gelatinase-associated lipocalin: prognostic value in patients with ST-segment elevation myocardial infarction treated with a primary percutaneous coronary intervention.

BACKGROUND: There are no previous data on serial changes in neutrophil gelatinase-associated lipocalin (NGAL) levels in ST-segment elevation myocardial infarction (STEMI) patients before and after a primary percutaneous coronary intervention (pPCI). The aim of the present study was to evaluate the prognostic value of serial NGAL measurements in patients with STEMI treated by pPCI. MATERIALS AND METHODS: We identified 169 STEMI patients who underwent pPCI within 12 h of symptom onset and had plasma NGAL measurements before (pre-NGAL) and 6 h after (post-NGAL) pPCI. The primary endpoint was 30-day all-cause mortality, including cardiac death, whereas the secondary endpoint was the change in NGAL levels from before to after pPCI. RESULTS: The mean pre-NGAL and post-NGAL levels were 109.2±76.1 and 93.3±83.8 ng/ml, respectively. Thirty-day mortality occurred in 12 (7.1%) patients. In terms of changes in serial NGAL levels, post-NGAL levels were decreased in 132 (79%) patients. Patients with elevated post-NGAL levels showed increased mortality compared with patients with decreased post-NGAL levels (P=0.005). Multivariate analyses indicated that old age and high post-NGAL levels were independent risk factors for 30-day mortality. CONCLUSION: In a large percentage of STEMI patients, plasma post-pPCI NGAL levels were decreased compared with pre-pPCI NGAL levels, even with the administration of potentially nephrotoxic contrast medium. Post-NGAL levels seemed to be superior to pre-NGAL levels for the prediction of 30-day mortality outcome.

A case of a resected benign myxoma-like hemorrhagic cyst, which later recurred as undifferentiated pleomorphic sarcoma in the left atrium.

RATIONALE: An intracardiac cystic mass is a rare type of mass found in the left atrium. The differential diagnosis of an intracardiac cystic mass includes hydatid cysts, bronchogenic cysts, intracardiac varices, and hemorrhages in some tumor types, including myxoma. PATIENT CONCERNS: We present the case of a 68-year-old woman who presented with episodic dyspnea. DIAGNOSES-INTERVENTIONS-OUTCOMES: Transthoracic echocardiography (TTE) revealed the presence of a left atrial mass mimicking myxoma. However, in postoperative findings, it was determined that the mass was actually a hemorrhagic cyst. Eighteen months later, the patient presented with recurrent exertional dyspnea and TTE revealed the recurrence of a left atrial mass. Computed tomography showed that the mass extended into the right atrium, inferior vena cava, and coronary sinus. After re-operation, the final histological diagnosis was determined to be an undifferentiated pleomorphic sarcoma in the left atrium. LESSONS: An intracardiac hemorrhagic cyst was suspected during the operation of a benign-looking LA mass. As such, we recommend that other rare etiologies be considered and more biopsies be performed when possible.

miRNA polymorphisms (miR­146a, miR­149, miR­196a2 and miR­499) are associated with the risk of coronary artery disease.

Small non­coding microRNAs (miRNAs) are not only important for heart and vascular development but are also important in cardiovascular pathophysiology and diseases, such as ischemia and atherosclerosis­related diseases. However, the effect of miR­146a, miR­149, miR­196a2 and miR­499 polymorphisms on coronary artery disease (CAD) susceptibility remain unknown. The aim of the present study was to examine the genotype frequencies of miR­146a, miR­149, miR­196a2 and miR­499 polymorphisms in patients with CAD, and assess their clinical applications for diagnosing and monitoring CAD. Using polymerase chain reaction­amplified DNA, microRNA polymorphisms were analyzed in 522 patients with CAD and 535 control subjects. The miR­149 rs2292832 C>T and miR­196a2 rs11614913 T>C polymorphisms were shown to be significantly associated with CAD prevalence. In subgroup analyses according to disease severity, the miR­146a rs2910164GG genotype was significantly associated with CAD risk in the stent ≥2 group. In addition, miR­146aG/­149T/­196a2C/­499 G allele combination was significantly associated with CAD prevalence (G­T­C­G and G­C­C­G of miR­146a/­149/­196a2/­499). The combination genotypes of miR­146aGG/149TC+CC and miR­149CC/196a2TC were significantly associated with CAD incidence. In subgroup analyses, miR­146a rs2910164 C>G increased the risk of developing CAD in non­smoking, hypertensive and nondiabetic subgroups. Furthermore, miR­149 rs2292832 C>T and miR­196a2 rs11614913 T>C was shown to increase CAD risk in females and patients aged >63 years old. The miR­149T allele, miR­196a2C allele and miR­146aG/­149T/­196a2C/­499 G allele combination were associated with CAD pathogenesis. The combined effects of environmental factor and genotype combination of miRNA polymorphisms may contribute to CAD prevalence.

Prognostic value of preoperative N-terminal pro-brain natriuretic peptide in non-cardiac surgery of elderly patients with normal left ventricular systolic function.

AIM: We investigated the prognostic value of preoperative N-terminal pro-brain natriuretic peptide (NT-proBNP) in non-cardiac surgery in elderly patients who showed normal left ventricular function on preoperative echocardiography. METHODS: We analyzed 1459 patients aged older than 70 years who had consulted a cardiologist for the evaluation of cardiovascular risk for non-cardiac surgery. Of the 721 patients who simultaneously underwent echocardiography and NT-proBNP assessments, 506 who showed normal left ventricular systolic function were included. The predictive power of NT-proBNP for the risk of major adverse cardiac and cerebrovascular events (MACCE) was evaluated. RESULTS: MACCE occurred in 40 (7.9%) of the 506 patients, and the median value of NT-proBNP was higher in patients with complications than in those without (MACCE group: 1700.5 pg/mL vs non MACCE group: 206.35 pg/mL; P < 0.001). The area under the receiver operating characteristic curve was 0.804 (P < 0.001), with an optimal cut-off of 425.3 pg/mL. Multivariate analysis showed that increased NT-proBNP (>425.3 pg/mL; odds ratio 6.381; P < 0.001) was the only independent risk factor for the prediction of MACCE. CONCLUSIONS: In elderly patients who showed normal left ventricular systolic function on echocardiography, measurement of preoperative NT-proBNP concentration might be a useful test for predicting the occurrence of MACCE after non-cardiac surgery. Geriatr Gerontol Int 2016; 16: 1109-1116.

Association of insulin resistance and coronary artery remodeling: an intravascular ultrasound study.

BACKGROUND: There are few studies that investigated the correlation between insulin resistance (IR) and the coronary artery remodeling. The aim of the study is to investigate the association of IR measured by homeostasis model assessment of insulin resistance (HOMA-IR) and coronary artery remodeling evaluated by intravascular ultrasound (IVUS). METHODS: A total of 298 consecutive patients who received percutaneous coronary interventions under IVUS guidance were retrospectively enrolled. The value of HOMA-IR more than 2.5 was considered as IR positive. Metabolic syndrome was classified according to NCEP ATP III guidelines. The remodeling index was defined as the ratio of the external elastic membrane (EEM) area at the lesion site to the EEM area at the proximal reference site. RESULTS: A total of 369 lesions were analyzed (161 lesions in HOMA-IR positive and 208 lesions in HOMA-IR negative). Remodeling index was significantly higher in the HOMA-IR positive group compared with the negative group (HOMA-IR positive vs. negative: 1.074 ± 0.109 vs. 1.042 ± 0.131, p = 0.013). There was a significant positive correlation between remodeling index and HOMA-IR (p = 0.010). Analysis of HOMA-IR according to remodeling groups showed increasing tendency of HOMA-IR, and it was statistically significant (p = 0.045). Multivariate analysis revealed that only HOMA-IR was an independent predictor of remodeling index (r = 0.166, p = 0.018). CONCLUSION: Increased IR estimated by HOMA-IR was significantly associated with a higher remodeling index and positive coronary artery remodeling.

Impact of central haemodynamics on left ventricular function in individuals with an exaggerated blood pressure response to exercise.

OBJECTIVE: The impact of exaggerated blood pressure response (EBPR) to exercise on left ventricular function and the mechanism of its association are poorly understood. This study investigated the impact of arterial stiffening on left ventricular function in individuals with an EBPR to exercise. We hypothesized that individuals with low pulse pressure (PP) amplification during exercise would have worse left ventricular function than those with high PP amplification in individuals with an EBPR to exercise. METHODS: Fifty-nine individuals with an EBPR to exercise (18 men, age 57 ±â€Š12 years) and 59 age and sex-matched controls were studied. Radial artery tonometry was performed at rest and immediately after exercise during supine bicycle exercise echocardiography. RESULTS: There were no differences in left ventricular structure or function between individuals with an EBPR to exercise and controls. When individuals with an EBPR to exercise were divided into two groups on the basis of PP amplification after exercise [Group 1 (n = 30), high PP amplification after exercise; Group 2 (n = 29), low PP amplification after exercise], group 2 showed larger left atrial volume and lower early diastolic (e') and systolic (S') mitral annular velocities. Left ventricular apical rotation was also exaggerated in group 2. In multiple regression, PP amplification after exercise was an independent determinant of e' (ß = 0.16, P = 0.019) and S' (ß = 0.25, P = 0.009) in individuals with an EBPR to exercise. CONCLUSION: In individuals with an EBPR to exercise, the degree of left ventricular dysfunction is variable. EBPR to exercise in the presence of arterial stiffening contributes to the deterioration of left ventricular function.

Non-invasive assessment of vascular alteration using ultrasound.

It is well known that arterial function relates to cardiovascular morbidity and mortality. The noninvasive technology for the assessment of arterial function has developed as the importance of prevention of early cardiovascular disease has been emphasized. Over 2-D and Doppler echocardiography, speckle-tracking echocardiography has emerged as a valuable ultrasound imaging technique that allows for an objective and quantitative evaluation of global and regional myocardial function. Recently, several studies have extended its applicability beyond cardiac chambers, such as artery. Measurement of carotid arterial strain with speckle tracking ultrasound has been shown to be feasible and reliable. This review describes the new ultrasound techniques to assess arterial function and their clinical implications.

Delayed embolisation of amplatzer ASD closure device caused partial obstruction of left ventricular outflow tract.

A 54-year-old male presented with symptoms of dyspnoea, and oedema of the lower extremities. Transthoracic echocardiography (TTE) revealed secondum-type atrial septal defect (ASD). He successfully received a 30-mm Amplatzer ASD closure device percutaneously. Echocardiography immediately after the procedure and the next day showed a well-positioned device. He was discharged the next day on 100 mg aspirin daily and warfarinisation due to atrial fibrillation. A month later, he revisited the hospital due to recurrence of dyspnoea and a grade 2 systolic murmur was heard on the left parasternal border. A chest X-ray showed abnormal location of the closure device and TTE revealed re-appearance of the ASD and an embolised Amplatzer device in the left ventricular outflow tract (LVOT) with partial obstruction. He requested surgery to remove the Amplatzer device and received an ASD patch repair, tricuspid valve repair and modified Maze operation concurrently. He is now in routine follow up without any other complications.

An exaggerated blood pressure response to exercise is associated with subclinical myocardial dysfunction in normotensive individuals.

OBJECTIVES: An exaggerated blood pressure (BP) response to exercise is associated with adverse cardiovascular outcomes, even in normotensive individuals. The purpose of this study was to compare myocardial function between normotensive individuals with and without an exaggerated BP response. METHODS: We evaluated global myocardial function using speckle tracking echocardiography in normotensive individuals. Two-dimensional speckle tracking echocardiography and a treadmill exercise test were performed simultaneously in 171 normotensive individuals (mean age: 48 ±â€Š8 years; 97 men) without any structural heart disease. RESULTS: Among 171 normotensive individuals, 19 (11%) exhibited an exaggerated BP response (≥200  mmHg for men and ≥190  mmHg for women) during the treadmill test. Conventional echocardiographic parameters were similar between the two groups. However, on strain analyses, the systolic and early diastolic global longitudinal strains of the left ventricle (LV) and left atrium were lower in individuals with an exaggerated BP response to exercise. The peak SBP during exercise was inversely related to systolic global longitudinal strain of the LV (r = -0.35, P < 0.01) and left atrium (r = -0.41, P < 0.01). On multivariate analyses, an exaggerated BP response to exercise was shown to be an independent determinant of reduced global longitudinal strain of the LV (ß = -0.20, P < 0.05) and left atrium (ß = -0.28, P < 0.05). CONCLUSION: Normotensive individuals with an exaggerated BP response to exercise exhibit impairment in longitudinal myocardial function. Even without apparent hypertension, an exaggerated BP response could cause repeated increases in afterload and result in subclinical myocardial dysfunction.

Blocking the receptor for advanced glycation end product activation attenuates autoimmune myocarditis.

BACKGROUND: The Receptor for Advanced Glycation End Products (RAGE) is a pattern recognition receptor for endogenous ligands, and is associated with various inflammatory diseases. However, the role of RAGE activation in myocarditis has yet to be examined. The potential role of RAGE in the development of experimental autoimmune myocarditis (EAM) and the effect of RAGE blocking in attenuating the inflammation in the EAM was investigated. METHODS AND RESULTS: EAM was evoked in Lewis rats by immunization with porcine cardiac myosin. Soluble RAGE (sRAGE) was injected to block RAGE activation. Echocardiogram, histological, and immunohistochemical examinations were conducted on days 21 and 42. In rats with EAM, RAGE expression in cardiac tissue was prominent on day 21. Rats administered sRAGE during the early antigen-priming phase showed marked attenuation in acute and chronic inflammation compared with untreated rats. RAGE expression was significantly reduced in rats treated in the early phase. However, sRAGE administration, after the initial antigen-priming phase, failed to ameliorate EAM development. CONCLUSIONS: RAGE expression was significantly increased in the heart during EAM. Blocking RAGE activation with sRAGE during the early antigen-priming phase reduced acute and chronic inflammation and improved cardiac function. In contrast, blocking RAGE after the early phase did not attenuate EAM development. These results imply that RAGE is involved in regulating innate immune responses during the early phase of myocarditis development.

Traumatic aortic regurgitation combined with descending aortic pseudoaneurysm secondary to blunt chest trauma.

Rupture of the aorta is a relatively rare complication of blunt chest trauma, and traumatic rupture of the aortic valve is even rarer. Even though both result from blunt chest trauma, the causative mechanisms of aortic valve injury differ from those of descending aortic rupture. There are no previous reports in the literature of simultaneous injuries to both the descending aorta and the aortic valve. We report a case of a 70-year-old man who presented with traumatic aortic regurgitation combined with traumatic pseudoaneurysm of the aortic isthmus following blunt chest trauma, and its successful repair with a hybrid surgical strategy.

High prevalence of unrecognized chordae tendineae rupture in mitral valve prolapse patients undergoing valve replacement surgery.

BACKGROUND: Not infrequently, chordae tendineae rupture, which was not recognized preoperatively using echocardiography, was found during mitral valve (MV) surgery in patients with severe mitral regurgitation (MR) diagnosed with MV prolapse. We evaluated the incidence and predictors of echocardiographically-unrecognized chordae tendineae rupture in patients with severe MR because of MV prolapse. METHODS: We enrolled 124 patients undergoing MV surgery for severe MR because of nonrheumatic MV prolapse. Patients with MR because of infective endocarditis, ischemic heart disease, or echocardiographically-detected chordal rupture were excluded. The study sample was divided into 2 groups: surgically-proven chordae tendineae rupture (n = 51), and no chordae rupture (n = 73). RESULTS: Echocardiographically-unrecognized chordae tendineae rupture was found in 51 (41%) of 124 patients undergoing MV surgery because of MR. It was more common in patients with posterior or single-leaflet prolapse. Although the severity of MR was greater in patients with chordal rupture, left atrial volume index was smaller compared with those without. In a multivariate analysis, involvement of posterior leaflet (odds ratio [OR], 2.80; 95% confidence interval [CI], 1.15-6.84) or single leaflet (OR, 3.18; 95% CI, 1.07-9.45), MR severity (OR, 4.76; 95% CI, 1.96-11.59), and left atrial volume index (OR, 0.98; 95% CI, 0.96-0.99) were independently associated with chordal rupture (P < 0.05 for all). CONCLUSIONS: Unrecognized chordae tendineae rupture is a common unrecognized contributor to severe MR necessitating valve replacement in MV prolapse patients. Earlier recognition and more specific management might contribute to improved prognosis for such patients.