Wnt Signaling Inhibition Prevents Postnatal Inflammation and Disease Progression in Mouse Congenital Myxomatous Valve Disease.

BACKGROUND: Myxomatous valve disease (MVD) is the most common cause of mitral regurgitation, leading to impaired cardiac function and heart failure. MVD in a mouse model of Marfan syndrome includes valve leaflet thickening and progressive valve degeneration. However, the underlying mechanisms by which the disease progresses remain undefined. METHODS: Mice with Fibrillin 1 gene variant Fbn1C1039G/+ recapitulate histopathologic features of Marfan syndrome, and Wnt (Wingless-related integration site) signaling activity was detected in TCF/Lef-lacZ (T-cell factor/lymphoid enhancer factor-ß-galactosidase) reporter mice. Single-cell RNA sequencing was performed from mitral valves of wild-type and Fbn1C1039G/+ mice at 1 month of age. Inhibition of Wnt signaling was achieved by conditional induction of the secreted Wnt inhibitor Dkk1 (Dickkopf-1) expression in periostin-expressing valve interstitial cells of Periostin-Cre; tetO-Dkk1; R26rtTA; TCF/Lef-lacZ; Fbn1C1039G/+ mice. Dietary doxycycline was administered for 1 month beginning with MVD initiation (1-month-old) or MVD progression (2-month-old). Histological evaluation and immunofluorescence for ECM (extracellular matrix) and immune cells were performed. RESULTS: Wnt signaling is activated early in mitral valve disease progression, before immune cell infiltration in Fbn1C1039G/+ mice. Single-cell transcriptomics revealed similar mitral valve cell heterogeneity between wild-type and Fbn1C1039G/+ mice at 1 month of age. Wnt pathway genes were predominantly expressed in valve interstitial cells and valve endothelial cells of Fbn1C1039G/+ mice. Inhibition of Wnt signaling in Fbn1C1039G/+ mice at 1 month of age prevented the initiation of MVD as indicated by improved ECM remodeling and reduced valve leaflet thickness with decreased infiltrating macrophages. However, later, Wnt inhibition starting at 2 months did not prevent the progression of MVD. CONCLUSIONS: Wnt signaling is involved in the initiation of mitral valve abnormalities and inflammation but is not responsible for later-stage valve disease progression once it has been initiated. Thus, Wnt signaling contributes to MVD progression in a time-dependent manner and provides a promising therapeutic target for the early treatment of congenital MVD in Marfan syndrome.

Evaluation of cardiac beat synchronization control for a rotary blood pump on valvular regurgitation with a mathematical model.

We have studied the cardiac beat synchronization (CBS) control for a rotary blood pump (RBP) and revealed that it can promote pulsatility and reduce cardiac load. Besides, patients with LVAD support sometimes suffer from aortic and mitral regurgitation (AR and MR). A control method for the RBP should be validated in wider range of conditions to clarify its benefits and pitfalls prior to clinical application. In this study, we evaluated pulsatility and cardiac load reduction obtained with the CBS control on valvular failure conditions with a mathematical model. Diastolic assist could reduce cardiac load on the left ventricle by decreasing external work of the ventricle even in MR cases while it was not so effective in AR cases. Systolic assist can still promote pulsatility in AR and MR cases; however, aortic valve function should be carefully confirmed since pulse pressure can be wider not due to systolic assist but to AR.

Mild Ischemic Mitral Regurgitation: Is Revascularization Enough for Every Patient?

BACKGROUND: The progress of mild ischemic mitral regurgitation (MR) after isolated coronary artery bypass is not clear. We aimed to determine the proportion of patients with mild ischemic MR undergoing isolated coronary artery bypass grafting (CABG) presenting with regression of or persistent MR one year after CABG and to identify the significantly different echocardiographic variables between regressing and persistent MR. METHODS: Sixty-three patients with preoperative mild ischemic MR were categorized into an MR- regression or an MR-persistence group one year after isolated CABG. The echocardiographic indices, indicating mitral leaflet configuration and remodeling of the left ventricle (LV), were measured before and one year after the surgery. RESULTS: One year after CABG, MR regressed in 60% (38/63) and persisted in 40% (25/63) of the patients. The left ventricular diameter, volume, and sphericity and anteroposterior diameter of the mitral annulus improved only in the MR-regression group, while the ejection fraction improved in both groups (47.7% ± 12.4% from 40.1% ± 11.3%, P < .001 in the regression group and 43.2% ± 14.0% from 39.3% ± 11.6%, P = .035 in the persistence group). A >15% decrease in the LV end-systolic volume was noted more frequently in the MR-regression group (60.5% versus 30%, P = .027). The leaflet angle did not show asymmetry or significant changes in both groups. CONCLUSIONS: Isolated CABG improved mild MR in most patients with mild ischemic MR. These patients showed greater reverse remodeling after revascularization than the patients with persistent MR after isolated CABG. Additional tests, which can predict LV reverse remodeling, are needed to predict persistent MR.

[Video Assisted Left Ventricular Pseudoaneurysm Repair].

An 80-year-old male was admitted to our hospital because of subacute myocardial infarction with moderate mitral regurgitation. Though he recovered well and went home within 2 weeks, the transthoracic echocardiography revealed rapid growing aneurysmal changes at the left ventricular posterior wall. We made diagnose of a pseudoaneurysm by the multi detector-row computed tomography, and planed a surgical treatment. Following the cardiac arrest, an endoscope was inserted into the left ventricle, we inspected the relation between the mitral valve and papillary muscles to detect proper suture lines and to avoid the mitral regurgitation. The defect of the left ventricular wall was repaired with 2-layer bovine pericardial patches reinforced with fibrin glue. His postoperative course was uneventful, and he was discharged from hospital on 12th postoperative day. We consider that inspections of intra-ventricle apparatus with the endoscope are useful to prevent the mitral valve insufficiency and keep the optimal left ventricle shape.

Early and medium-term outcomes of Alfieri mitral valve repair in the management of systolic anterior motion during septal myectomy.

BACKGROUND: This report studies the early and medium-term clinical and echocardiographic outcomes of the Alfieri edge-to-edge mitral valve repair, as adjunctive therapy, to prevent and treat systolic anterior motion (SAM) at the time of septal myectomy (SM) for left ventricular outflow tract obstruction in hypertrophic cardiomyopathy. METHODS: From 2009-2015, 11 consecutive patients had a trans-atrial Alfieri repair, to prevent (n = 7) or treat (n = 4) SAM at the time of SM. RESULTS: No patients were lost to follow-up. There were no perioperative or late deaths. Pre-bypass, the mean left ventricular outflow tract gradient, measured directly by simultaneous needle insertion, was 40.7 ± 19.9 mmHg at rest and 115.8 ± 30.4 mmHg on provocation with Isoproterenol, which reduced after SM and Alfieri repair and discontinuation of bypass, to a mean gradient of 8.3 ± 9.8 mmHg at rest and 25.8 ± 9.2 mmHg on provocation. One patient who required mitral valve replacement on day 4, was hospitalized at 2.7 years with heart failure requiring diuresis and remains well at 6 years. One patient developed postoperative atrial fibrillation. There were no other early or late complications. At a median follow-up of 6.6 years (international quartile range 1.2-7.4), clinical and echocardiographic data demonstrated maintained improvement in mean New York Heart Association class from 2.6 ± 0.9 preoperatively to 1.7 ± 0.4 and reduction in mean grade of mitral regurgitation from 2.7 ± 0.8 preoperatively to 0.7 ± 0.6. CONCLUSIONS: The Alfieri repair, as adjunctive therapy, for the prevention or treatment of SAM at the time of SM demonstrates satisfactory early and medium-term clinical and echocardiographic outcomes supporting the ongoing utility of this approach.

Beneficial effects of a cardiac support device on left ventricular remodeling after posterior myocardial infarction: an evaluation by echocardiography, pressure-volume curves and ventricular histology.

PURPOSE: Posterior myocardial infarction (MI) can induce LV remodeling and ischemic mitral regurgitation (IMR). The protective effects of a cardiac support device (CSD) against LV remodeling and IMR after posterior MI have been poorly documented. METHODS: Posterior MI was induced by ligation of the left circumflex coronary artery in beagle dogs. After 7 days, the dogs were randomized to a CSD placement (CSD group, n = 8) or no treatment (CTL group, n = 8). RESULTS: At 3 months after MI, the LV remodeling was less marked and the LV and RV systolic functions were better in the CSD group than in the CTL group. Neither the RV nor LV diastolic function (min dP/dt, Tau and EDPVR) was disturbed by the CSD. IMR was consistently prevented in our canine model. CONCLUSION: Early application of a CSD after posterior MI can attenuate LV remodeling without causing any deterioration of the biventricular diastolic function.

The effects of right ventricular apical pacing with transvenous pacemaker and implantable cardioverter defibrillator on mitral and tricuspid regurgitation.

BACKGROUND: The incidence of new or worsening tricuspid regurgitation (TR) or mitral regurgitation (MR) after permanent pacemaker (PPM) or implantable cardioverter defibrillator (ICD) lead placement has not been well investigated. We studied the effect of transvenous leads implantation and right ventricular (RV) pacing on tricuspid and mitral valve regurgitations. METHODS: We reviewed the charts of all patients undergoing PPM or ICD lead placement in our electrophysiology laboratory from December 2001 to December 2006. RESULTS: A total of 206 patients (120 with PPM and 86 with ICD) had baseline echocardiography within 6months before, and a follow up study at least 6months after lead insertion. The mean age was 74±14years; 56% were men. The follow-up period was 29±19months. TR worsened by at least one grade after lead insertion in 44.7% patients (P<0.001). Pre- and post-implant changes in TR severity did not differ with respect to lead type (ICD vs. PPM) or degree of RV pacing dependence. As for MR; patients with high frequency of RV pacing (>40%) had a higher incidence of worsening MR when compared to those with low frequency of RV pacing (44% vs. 19%; P<0.001). CONCLUSION: PPM or ICD lead implantation worsens TR; that effect is probably induced by mechanical interferences with the TV closure and was consistent regardless the lead type or degree of RV Pacing. MR was noted to increase in patients with high frequency of RV pacing frequency; this is probably caused by the mechanical dyssynchrony induced by RV pacing.

Efficacy of mitral valve repair as an adjunct procedure to coronary artery bypass grafting in moderate ischemic mitral regurgitation: a meta-analysis of randomized trials.

OBJECTIVE: Whether moderate ischemic mitral regurgitation (IMR) should be repaired during coronary artery bypass grafting (CABG) is still uncertain. This meta-analysis of randomized controlled trials (RCTs) evaluated the efficacy of adding mitral valve repair (MVR) to CABG in patients with moderate IMR. METHODS: We searched PubMed, the Cochrane Library, and the Web of Science for RCTs that compared the efficacy of CABG plus MVR with CABG alone. Four RCTs that included 505 patients met the eligibility criteria. RESULTS: CABG + MVR significantly reduced the risk of intermediate residual mitral regurgitation (MR) grade ≥2+ compared with CABG alone (risk ratio [RR] = 0.20, 95% confidence interval [CI] 0.04-0.92, p = 0.04), but did not have advantages on 30-day/in-hospital mortality (RR = 1.06, 95% CI 0.37-3.09, p = 0.91), intermediate mortality (RR = 0.90, 95% CI 0.48-1.67, p = 0.73), risk of intermediate NYHA class ≥II (RR = 0.62, 95% CI 0.24-1.62, p = 0.33), intermediate left ventricular ejection fraction (LVEF) (SMD = 0.04%, 95% CI -0.35 to 0.42, p = 0.84), and intermediate LV end-systolic volume index (LVESVI) (SMD = -0.20 mL/m(2) , 95% CI -0.92 to 0.51, p = 0.58). CONCLUSION: Compared with CABG alone, adding MVR to CABG in patients with moderate IMR reduces the residual MR grade, but has no significant effect on mortality, intermediate NYHA class, LVEF, and LVESVI. Further RCTs with larger sample size and longer follow-up are needed to more clearly elucidate the efficacy of MVR as an adjunct procedure to CABG in patients with moderate IMR.

Preventive strategies to fight complications during percutaneous multitrack balloon valvotomy "refining the technique".

BACKGROUND: Percutaneous mitral valvuloplasty (PMV) is still the treatment of choice in selected cases of mitral stenosis (MS). Multitrack balloon (MTB) catheter is one of the techniques used for PMV with optimal results. We describe a novel refinement of appropriate balloon sizing and wire placement to reduce mitral regurgitation (MR) and Left ventricular (LV) apical perforation, respectively. METHODS: Ninety four consecutive patients with moderate to severe rheumatic mitral stenosis (MS) were selected for PMV with MTB catheter. Balloon sizing was done by effective balloon dilatation area (EBDA), using standard geometric formula. 0.35" PMV wire was placed in aortic arch /ascending aorta (AA) to avoid LV apical perforation. RESULTS: Mild MR was present in 28(29.8%). Post-procedure MR was present in 50(53.2%). Out of 50 MR cases 44(88%) had mild and 6(12.0%) had moderate MR. No patient had severe MR. With placement of wire in AA and arch of aorta none of the patients developed complication of LV apical perforation. CONCLUSION: EDBA as balloon sizing for multitrack system can be used to reduce severity of mitral regurgitation. Placement of PMV guide wire in Aortic arch/AA ascending aorta can eliminate/substantially reduce dreadful complication of LV perforation.

[Perioperative management for patients with hypertrophic cardiomyopathy].

Hypertrophic cardiomyopathy is a common inherited cardiovascular disease present in one in 500 of the general population. It is caused by more than 1,400 mutations in 11 or more genes encoding proteins of the cardiac sarcomere. In the absence of evidence of any other cardiac or systemic disease that could have resulted in the hypertrophic event, diagnosis of hypertrophic cardiomyopathy requires a hypertrophied non-dilated left ventricle. It is associated with a significant risk for anesthesia. During anesthesia in patients diagnosed with hypertrophic cardiomyopathy, it is essential to maintain relatively slow heart rate, prevent hypovolemia, maintain or increase systemic vascular resistance, and avoid propofol as the sole anesthetic agent. Hence, balanced anesthesia is preferable in these patients. Furthermore, transesophageal echocardiography is very useful for intraoperative assessment and development of a strategy for improving left ventricular outflow tract obstruction (LVOTO) and mitral regurgitation (MR). LVOTO with MR resulting from systolic anterior motion (SAM) of the mitral valve often leads to hemodynamic collapse. Although patients who develop SAM have been managed with intravenous volume loading, reduction/discontinuation of inotropic drugs, and increasing afterload, these strategies have often been ineffective. Beta blockers and cibenzoline, an antiarrhythmic drug, decrease myocardial contraction, attenuate SAM, and improve hemodynamics.

Permanent His-bundle pacing maintains long-term ventricular synchrony and left ventricular performance, unlike conventional right ventricular apical pacing.

AIMS: Right ventricular apical pacing (RVAP) may be deleterious, determining abnormal left ventricular (LV) electrical activation and progressive LV dysfunction. Permanent His-bundle pacing (HBP) has been proposed to prevent this detrimental effect. The aim of our study was to compare the long-term effects of HBP on LV synchrony and systolic performance with those of RVAP in the same group of patients. METHODS: Our analysis included 26 patients who received both an HBP lead and an RVAP lead, as backup, in our electrophysiology laboratory between 2004 and 2007. After implantation, all devices were programmed to obtain HBP. An intra-patient comparison of the effects of HBP and RVAP on LV dyssynchrony and function was performed at the last available follow-up examination. RESULTS: After a mean of 34.6 ± 11 months, the pacing modality was temporarily switched to RVAP. During RVAP, LV ejection fraction significantly decreased (50.1 ± 8.8% vs. 57.3 ± 8.5%, P < 0.001), mitral regurgitation significantly increased (22.5 ± 10.9% vs.16.3 ± 12.4%; P = 0.018), and inter-ventricular delay significantly worsened (33.4 ± 19.5 ms vs. 7.1 ± 4.7 ms, P = 0.003) in comparison with HBP. However, the myocardial performance index was not statistically different between the two pacing modalities (P = 0.779). No asynchrony was revealed by tissue Doppler imaging during HBP, while during RVAP the asynchrony index was significantly higher in both the four-chamber (125.8 ± 63.9 ms; P = 0.035 vs. HBP) and two-chamber (126 ± 86.5 ms; P = 0.037 vs. HBP) apical views. CONCLUSION: His-bundle pacing has long-term positive effects on inter- and intra-ventricular synchrony and ventricular contractile performance in comparison with RVAP. It prevents asynchronous pacing-induced LV ejection fraction depression and mitral regurgitation.

Long-term efficacy of hematopoietic stem cell transplantation on brain involvement in patients with mucopolysaccharidosis type II: a nationwide survey in Japan.

Hematopoietic stem cell transplantation (HSCT) has not been indicated for patients with mucopolysaccharidosis II (MPS II, Hunter syndrome), while it is indicated for mucopolysaccharidosis I (MPS I) patients <2 years of age and an intelligence quotient (IQ) of ≥ 70. Even after the approval of enzyme replacement therapy for both of MPS I and II, HSCT is still indicated for patients with MPS I severe form (Hurler syndrome). To evaluate the efficacy and benefit of HSCT in MPS II patients, we carried out a nationwide retrospective study in Japan. Activities of daily living (ADL), IQ, brain magnetic resonance image (MRI) lesions, cardiac valvular regurgitation, and urinary glycosaminoglycan (GAG) were analyzed at baseline and at the most recent visit. We also performed a questionnaire analysis about ADL for an HSCT-treated cohort and an untreated cohort (natural history). Records of 21 patients were collected from eight hospitals. The follow-up period in the retrospective study was 9.6 ± 3.5 years. ADL was maintained around baseline levels. Cribriform changes and ventricular dilatation on brain MRI were improved in 9/17 and 4/17 patients, respectively. Stabilization of brain atrophy was shown in 11/17 patients. Cardiac valvular regurgitation was diminished in 20/63 valves. Urinary GAG concentration was remarkably lower in HSCT-treated patients than age-matched untreated patients. In the questionnaire analysis, speech deterioration was observed in 12/19 patients in the untreated cohort and 1/7 patient in HSCT-treated cohort. HSCT showed effectiveness towards brain or heart involvement, when performed before signs of brain atrophy or valvular regurgitation appear. We consider HSCT is worthwhile in early stages of the disease for patients with MPS II.

Impact of mitral regurgitation on the outcome of patients treated with CRT-D: data from the InSync ICD Italian Registry.

BACKGROUND: We assessed the influence of clinically significant mitral regurgitation (MR) on clinical-echocardiographic response and outcome in heart failure (HF) patients treated with a biventricular defibrillator (cardiac resynchronization therapy defibrillator [CRT-D]). METHODS AND RESULTS: A total of 659 HF patients underwent successful implantation of CRT-D and were enrolled in a multicenter prospective registry (median follow-up of 15 months). Following baseline echocardiographic evaluation, patients were stratified into two groups according to the severity of MR: 232 patients with more than mild MR (Group MR+: grade 2, 3, and 4 MR) versus 427 patients with mild (grade 1) or no functional MR (Group MR-). On 6- and 12-month echocardiographic evaluation, MR was seen to have improved in the vast majority of MR+ patients, while it remained unchanged in most MR- patients. On 12-month follow-up evaluation, a comparable response to CRT was observed in the two groups, in terms of the extent of left ventricular reverse remodeling and combined clinical and echocardiographic response. During long-term follow-up, event-free survival did not differ between MR+ and MR- patients, even when subpopulations of patients with ischemic heart disease and with dilated cardiomyopathy were analyzed separately. On multivariate analysis, the only independent predictor of death from any cause was the lack of ß-blocker use. CONCLUSIONS: This observational analysis supports the use of CRT-D in HF patients with clinically significant MR; MR had no major influence on patient outcome.

Levitronix CentriMag pump as perioperative left ventricular support in a patient with critical aortic stenosis, mitral regurgitation, and cardiogenic shock.

Severe aortic stenosis (AS) has a poor prognosis when associated with left ventricular dysfunction and congestive heart failure. Despite a relatively high operative mortality, most patients with severe AS and a depressed left ventricular ejection fraction (LVEF) should be considered candidates for aortic valve replacement. The CentriMag left ventricular assist system (Levitronix) can be used for perioperative or postcardiotomy circulatory support for the failing heart. In this case report, we report the successful use of the Levitronix CentriMag device as perioperative support in a high-risk patient with severe AS, significant mitral insufficiency, and a poor LVEF with advanced organ failure.

Predictors of residual mitral regurgitation after left ventricular assist device implantation.

Patients with advanced heart failure often have functional mitral regurgitation. Left ventricular assist device implantation improves functional mitral regurgitation through left ventricular unloading. However, residual mitral regurgitation after left ventricular assist device implantation leads to adverse outcomes, and whether patients need concomitant mitral valve surgery is not fully elucidated. Therefore, this study aimed to elucidate the predictors of residual mitral regurgitation and to describe the temporal changes in residual mitral regurgitation. We retrospectively enrolled 15 patients with implantable continuous-flow left ventricular assist device, who had significant mitral regurgitation on echocardiography before left ventricular assist device implantation. Three patients had residual mitral regurgitation (mitral regurgitation color jet area/left atrial area >0.2) 1 month after left ventricular assist device implantation. We investigated factors associated with residual mitral regurgitation and compared patients with or without residual mitral regurgitation. On univariate analysis, mitral valve tethering area and mitral regurgitation vena contracta before left ventricular assist device implantation were significantly associated with residual mitral regurgitation (odds ratio, 1.03; p = 0.036 and odds ratio, 10.45; p = 0.0087). One month after left ventricular assist device implantation, the mean pulmonary capillary wedge pressure and pulmonary artery pressure were higher in patients with residual mitral regurgitation (pulmonary capillary wedge pressure: 11.3 ± 3.5 vs 6.4 ± 3.4 mmHg, p = 0.029 and pulmonary artery pressure: 21.3 ± 4.0 vs 15.9 ± 3.3 mmHg, p = 0.023). However, the mitral regurgitation grading and hemodynamics were not significantly different 6 months after left ventricular assist device implantation. The hospitalization-free survival was not significantly different between the two groups. Mitral valve tethering area and mitral regurgitation vena contracta were predictors of residual mitral regurgitation. Residual mitral regurgitation improved until 6 months after left ventricular assist device implantation and might not affect the prognosis.

Primary percutaneous coronary intervention lowers the incidence of ischemic mitral regurgitation in patients with acute ST-elevated myocardial infarction.

BACKGROUND: The impact of primary percutaneous coronary intervention (PCI) for acute ST-elevated myocardial infarction (STEMI) on the incidence of ischemic mitral regurgitation (IMR) is unclear. METHODS AND RESULTS: Between January 2000 and December 2004, 318 patients presenting with first acute STEMI were enrolled in this study. Two hundred and twelve (66.67%) patients received PCI (PCI group), and 106 age- and Killip class-matched patients received medical management (non-PCI group). The median duration of follow up was 40.46 months. Compared to the non-PCI group, the PCI group had 14.6% (9.9% vs 24.5%) fewer patients with moderate or severe IMR (P<0.001). Univariate analysis demonstrated IMR was significantly associated with advanced age, higher Killip score, and posterior myocardial infarction (MI). Moreover, IMR was strongly associated with a lower left ventricular (LV) ejection fraction, larger left atrial dimension (LAd), and a larger LV end-systolic and LV end-diastolic volumes (LVEDV) (all P<0.01). Multivariate analysis revealed the odds of IMR in the PCI group was 0.208 times those of the non-PCI group (P<0.001). Additionally, moderate or severe IMR was independently correlated with advanced age, inferior MI, Killip class ≥3, larger LAd, and larger LVEDV (all P<0.05). Furthermore, long-term survival time was longer in the PCI group without IMR than in the non-PCI group with IMR (all P<0.01). CONCLUSIONS: PCI for first acute STEMI was associated with lower incidence of IMR. Advanced age, inferior MI, Killip class ≥3, larger LAd and LVEDV were risk factors associated with IMR development.

Left ventricular pseudoaneurysm arising between two papillary muscles: repair without mitral regurgitation.

Left ventricular pseudoaneurysm is a rare lesion that occurs when a contained free-wall rupture occurs after a transmural myocardial infarction. Such a pseudoaneurysm may be lethal if subsequent rupture or progressive heart failure occurs. We describe a 67-year-old man who, one year after undergoing coronary artery bypass grafting, developed an infero-apical left ventricular pseudoaneurysm between the bases of two papillary muscles without incurring significant mitral regurgitation. This was a highly unusual presentation. We were able to repair the aneurysm and restore normal mitral geometry without causing regurgitation.

Reduction in mitral regurgitation in patients undergoing cardiac resynchronization treatment: assessment of predictors by two-dimensional radial strain echocardiography.

BACKGROUND: We utilized the novel approach of 2D radial strain (2-DRS) to evaluate whether left ventricular (LV) mechanical dyssynchrony in mid-LV segments corresponding to papillary muscles insertion sites can predict early mitral regurgitation (MR) reduction post-cardiac resynchronization therapy (CRT). METHODS: We evaluated 32 patients undergoing CRT (mean age 64 +/- 17 years, 54% males) with MR grade > or =3 determined by the MR jet area/left atrial area ratio (JA/LAA). RESULTS: Fifteen (47%) patients responded to CRT (JA/LAA) < 25%). Sixty-seven percent of responders had mild or no residual MR and 33% had mild-to-moderate MR, while 70% of nonresponders had grade 3 or 4 MR (P = 0.0001) post CRT. The percent reduction in LV end-systolic volume was significantly higher in responders (P = 0.03), as was improvement in LVEF (P = 0.007). Significant delay of time-to-peak 2-DRS in the midposterior and inferior segments prior to CRT was found in responders compared with nonresponders (580 +/- 58 vs. 486 +/- 94, P = 0.002 and 596 +/- 79 vs. 478 +/- 127 ms, P = 0.005, respectively). Responders also had higher peak positive systolic 2-DRS in the posterior and inferior segments compared to nonresponders (22 +/- 13 vs. 12 +/- 7%, P = 0.01 and 17 +/- 9 vs. 9 +/- 7%, P = 0.02, respectively). Logistic regression analysis showed that the differences in pre-CRT inferoanterior time-to-peak 2-DRS of >110 ms and MRJA/LAA <40% as well as 2-DRS >18% in the posterior wall were significant predictors of post-CRT improvement in MR. CONCLUSION: The presence of a significant time-to-peak delay on 2-DRS between inferior and anterior LV segments, preserved strain of posterior wall, and MRJA/LAA <40% were found to be associated with significant MR reduction in patients post-CRT.

Worsening of left ventricular end-systolic volume and mitral regurgitation without increase in left ventricular dyssynchrony on acute interruption of cardiac resynchronization therapy.

BACKGROUND: Responders to cardiac resynchronization therapy (CRT) have greater left ventricular (LV) dyssynchrony than nonresponders prior to CRT. AIM: We conducted this study to see whether the long term responders have more worsening of LV dyssynchrony and LV function on acute interruption of CRT. MATERIALS AND METHODS: We identified 22 responders and 13 nonresponders who received CRT as per standard criteria for 23.73 +/- 7.9 months (median 24.5 months). We assessed the acute change in LV function, mitral regurgitation (MR) and compared LV dyssynchrony in CRT on and off modes. RESULTS: On turning off CRT, there was no significant worsening of LV dyssynchrony in both responders and nonresponders. The dyssynchrony measurements by SPWMD, TDI and 3D echocardiography did not correlate significantly. LVESV increased (p = 0.02) and MR (p = 0.01) worsened in CRT-off mode in responders only without significant change in LVEF or LV dimensions. DISCUSSION AND CONCLUSION: In long-term responders to CRT, there is alteration in the function of remodeled LV with acute interruption of CRT, without significant worsening of LV dyssynchrony. The role of different echocardiographic parameters in the assessment of LV dyssynchrony remains controversial. Even after long-term CRT reversely remodels the LV, the therapy needs to be continued uninterrupted for sustained benefits.

Reverse Remodeling of the Mitral Valve Complex After Radiofrequency Catheter Ablation for Atrial Fibrillation: A Serial 3-Dimensional Echocardiographic Study.

BACKGROUND: Mitral regurgitation is frequently complicated with atrial fibrillation without apparent organic changes in the leaflet, which occasionally improves after successful radiofrequency catheter ablation. We aimed to evaluate a possible geometric effect of radiofrequency catheter ablation on the mitral valve apparatus. METHODS: Forty-three consecutive patients who underwent successful catheter ablation for persistent atrial fibrillation (maintaining sinus rhythm for 6 months after their procedure) were examined by serial real-time 3-dimensional transesophageal echocardiography before and 6 months after catheter ablation. Mitral valve complex geometry was measured using dedicated software for 3-dimensional transesophageal echocardiography. RESULTS: Mitral valve apparatus showed significant reverse remodeling along with left atrial reverse remodeling 6 months after successful catheter ablation (50.5 [39.2-61.0] versus 36.4 [28.9-43.1] mL/m2; P<0.001). The degree of mitral regurgitation decreased in a majority of patients (mitral regurgitation jet area; 1.83 [0.78-3.09] versus 0.77 [0.36-1.47] cm2; P<0.001). Annular area significantly decreased (5.32±0.91 versus 4.73±0.76 cm2/m2; P<0.001) in both anterior-posterior and medial-lateral directions. Mitral annular contraction significantly recovered after maintaining sinus rhythm for 6 months (7.51 [4.82-9.62]% versus 9.71 [6.27-13.85]%; P=0.008). There were no significant changes in tenting volume or tenting height (0.46 [0.27-0.89] versus 0.51 [0.32-0.72] mL/m2, P=0.744; 2.34 [1.75-3.48] versus 2.76 [1.99-3.08] mm/m2, P=0.717). The leaflet surface area also significantly decreased after catheter ablation (5.74 [5.01-6.33] versus 5.19 [4.63-5.64] cm2/m2; P<0.001). CONCLUSIONS: Maintaining sinus rhythm after successful catheter ablation promotes reverse remodeling in the mitral valve apparatus and improves so-called atrial functional mitral regurgitation. The positive geometric effect of catheter ablation would be expected to be a possible contributor to better outcomes in patients with atrial fibrillation, in addition to the postprocedural freedom from rhythm disturbance.