Satoshi Kainuma

Does Stringent Restrictive Annuloplasty for Functional Mitral Regurgitation Cause Functional Mitral Stenosis and Pulmonary Hypertension

Background— It remains controversial whether restrictive mitral annuloplasty (RMA) for functional mitral regurgitation (MR) can induce functional mitral stenosis (MS) that may cause postoperative residual pulmonary hypertension (PH). Methods and Results— One hundred eight patients with left ventricular (LV) dysfunction and severe MR underwent RMA with stringent downsizing of the mitral annulus. Systolic pulmonary artery pressure (PAP) and mitral valve performance variables were determined by Doppler echocardiography prospectively and 1 month after RMA. Fifty-eight patients underwent postoperative hemodynamic measurements. Postoperative echocardiography showed a mean pressure half-time of 92±14 ms, a transmitral mean gradient of 2.9±1.1 mm Hg, and a mitral valve effective orifice area of 2.4±0.4 cm2, consistent with functional MS. Doppler-derived systolic PAP was 32±8 mm Hg, which correlated weakly with the transmitral mean gradient (&rgr;=0.23, P=0.02). Postoperative cardiac catheterization also showed significant improvements in LV volume and systolic function, pulmonary capillary wedge pressure, cardiac index, and systolic PAP; the latter was associated with LV end-diastolic pressure [standardized partial regression coefficient (SPRC)=0.51], pulmonary vascular resistance (SPRC=0.47), cardiac index (SPRC=0.37), and transmitral pressure gradient (SPRC=0.20). In a multivariate Cox proportional hazard model, postoperative PH (systolic PAP >40 mm Hg), but not mitral valve performance variables, was strongly associated with adverse cardiac events. Conclusions— RMA for functional MR resulted in varying degrees of functional MS. However, our data were more consistent with the residual PH being caused by LV dysfunction and pulmonary vascular disease than by the functional MS. The residual PH, not functional MS, was the major predictor of post-RMA adverse cardiac events.

Advanced left-atrial fibrosis is associated with unsuccessful maze operation for valvular atrial fibrillation

OBJECTIVE Atrial dilatation and fibrosis are considered to be important factors in the occurrence and maintenance of atrial fibrillation (AF). However, the relationship between those structural remodeling and postoperative sinus conversions after a maze operation has been rarely studied. The purpose of this study was to determine whether pathological evaluation of atrial tissues was useful for predicting an unsuccessful maze operation in patients with valvular AF. METHODS Between March 2006 and June 2007, left-atrial tissues in the posterior wall and right-atrial appendage were obtained from 47 consecutive patients (24 patients with chronic AF, and 23 with sinus rhythm) undergoing mitral valve surgery (MVS). A concomitant maze operation was performed for all patients with chronic AF. Atrial cell diameters were measured using hematoxylin and eosin staining, and quantitative assessment of atrial fibrosis was performed with Masson trichrome staining using an image analyzer (Image Processor for Analytical Pathology, Sumika Technoservice Co., Hyogo, Japan). RESULTS Successful MVS was performed for all patients and there were no complications associated with tissue sampling. Patients with chronic AF had more advanced histological features in both atria as compared with those with sinus rhythm. Sixteen of 24 patients, who underwent a maze operation, had successfully restored sinus rhythm (successful maze group), while that in the remaining eight was not restored (unsuccessful maze group). Patients in the unsuccessful maze group had a larger left-atrial dimension and cardiothoracic ratio as compared with those in the successful group, whereas the duration of AF was not significantly different. Patients in the unsuccessful maze group also had greater hypertrophy of cardiomyocytes and more extensive intercellular fibrosis in the left atrium, while there were no differences for right-atrial pathological features between the groups. Multivariate logistic analysis confirmed that a larger amount of left-atrial fibrosis (>15%) was significantly associated with an unsuccessful maze operation. CONCLUSIONS The present results suggested that advanced fibrosis in the left atrium, but not in the right atrium, might be significantly associated with an unsuccessful maze operation in patients with valvular AF.

Mechanism of Beneficial Effects of Restrictive Mitral Annuloplasty in Patients With Dilated Cardiomyopathy and Functional Mitral Regurgitation

Background— Restrictive mitral annuloplasty (RMA) often leads to reverse left ventricular (LV) remodeling in patients with advanced cardiomyopathy and functional mitral regurgitation. However, the mechanism responsible for its favorable effects on LV ejection performance has been poorly understood. We evaluated systolic wall stress using cineangiographic multidetector computed tomography (MDCT) and our developed software system to assess stress-shortening relations before and after RMA. Methods and Results— Twenty-four patients with dilated cardiomyopathy underwent 64-row MDCT before and 2 months after RMA. All patients underwent stringent downsizing annuloplasty with a semirigid complete ring. Reconstructed images were used to calculate LV end-diastolic index (EDVI) and end-systolic volume index (ESVI), LV ejection fraction, and regional and global end-systolic wall stress (ESS). After RMA, LVEDVI and LVESVI decreased from 151±52 to 131±53 mL/m2 (P=0.0001) and from 114±48 to 92±50 mL/m2 (P=0.0001), respectively. Global ESS decreased from 157±43 to 139±50 kdyne/cm2 (P=0.01), and LV ejection fraction improved from 27±8.0 to 33±13% (P=0.0007). There were significant correlations between change in LVEDVI and LVESVI (r=0.88, P<0.0001) and change in LVESVI and global ESS (r=0.68, P=0.0002). Moreover, the magnitude of increase in LV ejection fraction significantly correlated with the degree of reduction in global ESS (r=−0.61, P=0.002). Patients without significant reverse LV remodeling had significantly higher preoperative and postoperative global ESS than those with it. Conclusions— Our study suggests that decrease in afterload after reduction in volume overload was responsible for postoperative reverse LV remodeling process after RMA.

Cell-sheet Therapy With Omentopexy Promotes Arteriogenesis and Improves Coronary Circulation Physiology in Failing Heart

Cell-sheet transplantation induces angiogenesis for chronic myocardial infarction (MI), though insufficient capillary maturation and paucity of arteriogenesis may limit its therapeutic effects. Omentum has been used clinically to promote revascularization and healing of ischemic tissues. We hypothesized that cell-sheet transplantation covered with an omentum-flap would effectively establish mature blood vessels and improve coronary microcirculation physiology, enhancing the therapeutic effects of cell-sheet therapy. Rats were divided into four groups after coronary ligation; skeletal myoblast cell-sheet plus omentum-flap (combined), cell-sheet only, omentum-flap only, and sham operation. At 4 weeks after the treatment, the combined group showed attenuated cardiac hypertrophy and fibrosis, and a greater amount of functionally (CD31(+)/lectin(+)) and structurally (CD31(+)/α-SMA(+)) mature blood vessels, along with myocardial upregulation of relevant genes. Synchrotron-based microangiography revealed that the combined procedure increased vascularization in resistance arterial vessels with better dilatory responses to endothelium-dependent agents. Serial (13)N-ammonia PET showed better global coronary flow reserve in the combined group, mainly attributed to improvement in the basal left ventricle. Consequently, the combined group had sustained improvements in cardiac function parameters and better functional capacity. Cell-sheet transplantation with an omentum-flap better promoted arteriogenesis and improved coronary microcirculation physiology in ischemic myocardium, leading to potent functional recovery in the failing heart.

Pulmonary hypertension predicts adverse cardiac events after restrictive mitral annuloplasty for severe functional mitral regurgitation

OBJECTIVES Pulmonary hypertension (PH) is an indicator of a poor prognosis in patients with dilated cardiomyopathy. Few studies have investigated the prognostic role of PH in patients undergoing restrictive mitral annuloplasty (RMA) for severe functional mitral regurgitation secondary to advanced cardiomyopathy. METHODS A total of 46 patients undergoing RMA were classified into 3 groups on the basis of the Doppler-derived systolic pulmonary artery pressure (PAP) at baseline. Of the 46 patients, 19 had a systolic PAP less than 40 mm Hg (mild PH group), 17 had a systolic PAP of 40 to 60 mm Hg (moderate PH group), and 10 had a systolic PAP greater than 60 mm Hg (severe PH group). RESULTS Postoperative cardiac catheterization showed that the RMA procedure resulted in a significant reduction of the left ventricular (LV) preload and improvements in LV systolic function in all 3 groups, along with the relief of symptoms. During the follow-up period (mean, 36 ± 19 months), cardiac death occurred in 6 patients, readmission because of heart failure in 3, and fatal arrhythmia in 1. The rate of freedom from these cardiac events at 3 years was 93% ± 7%, 88% ± 8%, and 56% ± 17% in the mild, moderate, and severe PH groups (P < .001). Serial echocardiography showed that significant LV reverse remodeling occurred in 89%, 71%, and 25% of the mild, moderate, and severe PH groups, respectively. Multivariate Cox regression analysis identified severe PH (systolic PAP > 60 mm Hg) as a significant predictor of adverse cardiac events, as well as LV remodeling after RMA. CONCLUSIONS Noninvasive assessment of preoperative PH has a prognostic value in patients undergoing RMA for severe functional mitral regurgitation secondary to advanced cardiomyopathy.

Mitral Valve Repair for Medically Refractory Functional Mitral Regurgitation in Patients With End-Stage Renal Disease and Advanced Heart Failure

Background— Information regarding patient selection for mitral valve repair for chronic kidney disease or end-stage renal disease (ESRD) with severe heart failure (HF) as well as outcome is limited. Methods and Results— We classified 208 patients with advanced HF symptoms (Stage C/D) undergoing mitral valve repair for functional mitral regurgitation into 3 groups: estimated glomerular filtration rate ≥30 mL/min/1.73 m2 (control group, n=144); estimated glomerular filtration rate <30 mL/min/1.73 m2, not dependent on hemodialysis (late chronic kidney disease group, n=45), and ESRD on hemodialysis (ESRD group, n=19; preoperative hemodialysis duration 83±92 months). Follow-up was completed with a mean duration of 49±25 months. Postoperative (1-month) cardiac catheterization showed that left ventricular end-systolic volume index decreased from 109±38 to 79±41, 103±31 to 81±31, and 123±40 to 76±34 mL/m2, in the control, late chronic kidney disease, and ESRD groups, respectively. Left ventricular end-diastolic pressure decreased, whereas cardiac index increased in all groups with no intergroup differences for those postoperative values. Freedom from mortality and HF readmission at 5 years was 18%±7% in late chronic kidney disease (P<0.0001 versus control, P=0.01 versus ESRD), and 64%±12% in ESRD (P=1 versus control) as compared with 52%±5% in the control group (median event-free survival, 26, 67, and 63 months, respectively). Conclusions— Mitral valve repair for medically refractory functional mitral regurgitation in patients with advanced HF yielded improvements in left ventricular function and hemodynamics irrespective of preoperative renal function status. Patients with ESRD showed favorable late outcome in terms of freedom from mortality and readmission for HF as compared with those with late chronic kidney disease. Further studies are needed to assess the survival benefits of mitral valve repair in patients with ESRD and advanced HF.

Novel technique for reimplantation of intercostal arteries using tailored patch graft

We developed a simple and secure technique for reimplantation of the intercostal arteries (ICAs) using a patch graft during thoracoabdominal aneurysm repair. With our procedure, a sidearm branch with its base is tailored from a 24 mm one-branch Dacron graft, and then sutured as a patch graft to the trimmed wall of the descending aorta to cover the ICA orifices between Th9 and Th12. The proximal end of the patch graft is then anastomosed to the main tube graft, while the graft is perfused. With this technique, the entire suture lines are clearly visible and hemostasis is secured without difficulty. We used this technique in 6 patients, in whom 2.3+/-0.8 pairs of ICAs were reimplanted. The time required for reimplantation of the ICAs was 14+/-6 min and none of 6 patients developed paraplegia. Our results indicate that this novel technique is a simple method to obtain secure hemostasis under direct vision, which may contribute to reduce the risk of paraplegia during thoracoabdominal aneurysm repair.

B-type natriuretic peptide response and reverse left ventricular remodeling after surgical correction of functional mitral regurgitation in patients with advanced cardiomyopathy

BACKGROUND Restrictive mitral annuloplasty (RMA) can reverse left ventricular (LV) remodeling and reduce plasma B-type natriuretic peptide (BNP), a surrogate biomarker of heart failure. However, the relationship between reverse LV remodeling and plasma BNP changes after RMA is poorly defined. We explored the main hemodynamic factors contributing to change in plasma BNP after RMA in patients with functional mitral regurgitation (MR). METHODS Twenty-four patients with moderate to severe functional MR secondary to LV systolic dysfunction [ejection fraction (EF) <40%] underwent 64-row multidetector computed tomography (MDCT) before and 1.4 months after RMA. LV end-diastolic volume index (EDVI), end-systolic volume index (ESVI), LVEF, and regional and global end-systolic wall stress (ESS) were calculated from 3-dimensional MDCT images, with blood samples for plasma BNP measurement collected the same day. RESULTS After RMA, LV volumes and global ESS were decreased, while LVEF improved (all p<0.01). There were significant correlations between changes in LVEDVI and LVESVI (r=0.90, p<0.0001), LVESVI and global ESS (r=0.54, p=0.006), and global ESS and LVEF (r=-0.60, p=0.002). The median value for the plasma BNP also decreased from 597 pg/ml [interquartile range (IQR), 360-934 pg/ml] to 207 pg/ml (IQR, 124-271 pg/ml), in association with changes in LVEDVI (r=0.47, p=0.019), LVESVI (r=0.56, p=0.004), LVEF (r=-0.60, p=0.002), and global ESS (r=0.74, p<0.0001). Multivariate regression analysis showed that global ESS change was the strongest contributor to change in natural-log-transformed plasma BNP (standardized partial regression coefficient=0.59, p=0.004), indicating a strong association between decrease in LV afterload and reduction in plasma BNP level after RMA. CONCLUSIONS There may be a significant association between LV reverse remodeling and plasma BNP change after RMA. Furthermore, LV end-systolic myocardial stress may be the key mechanical stimulus influencing plasma BNP after surgical correction for functional MR. Whether these favorable BNP responses and reverse remodeling can predict improved survival requires further study.

Restrictive Mitral Annuloplasty With or Without Surgical Ventricular Restoration in Ischemic Dilated Cardiomyopathy With Severe Mitral Regurgitation

Background— We assessed changes in left ventricular (LV) volume and function and in regional myocardial wall stress in noninfarcted segments after restrictive mitral annuloplasty (RMA) with or without surgical ventricular restoration (SVR). Methods and Results— Thirty-nine patients with ischemic cardiomyopathy (ejection fraction ⩽0.35) and severe mitral regurgitation (≥3) were studied before and 2.8 months after surgery with cine-angiographic multidetector computed tomography (cine-MDCT). Eighteen underwent RMA alone (RMA group) and 21 underwent RMA and SVR (RMA+SVR group). In addition to measuring conventional parameters (LV end-diastolic volume index [LVEDVI], LV end-systolic volume index [LVESVI], and LV ejection fraction), we evaluated the regional circumferential end-systolic wall stress and mean circumferential fiber shortening in both the basal and mid-LV regions using 3-dimensional cine-MDCT images. LV end-diastolic and end-systolic volume indexes were significantly greater in the RMA+SVR group than in the RMA group preoperatively, but these values did not differ significantly postoperatively. LV end-diastolic and end-systolic volume indexes decreased significantly, by 21% and 27% after RMA and by 35% and 42% after RMA and SVR, and the percent reductions in LV end-diastolic and end-systolic volume indexes were significantly larger in the RMA+SVR group. Regional end-systolic wall stress decreased and circumferential fiber shortening increased significantly in the noninfarcted regions after RMA with or without SVR. Conclusions— RMA plus SVR showed a potentially greater reduction of LV end-diastolic and end-systolic volume indexes than RMA alone. In selected patients with more advanced LV remodeling, concomitant SVR may favorably affect the LV reverse-remodeling process induced by RMA.

Restrictive mitral annuloplasty with or without surgical ventricular reconstruction in ischaemic cardiomyopathy: impacts on neurohormonal activation, reverse left ventricular remodelling and survival.

In the STICH trial, adding surgical ventricular reconstruction (SVR) to coronary artery bypass grafting (CABG) reduced LV end‐systolic volume index (LVESVI) by 19%, as compared with 6% with CABG alone, providing no survival or functional benefits. Herein, we compared the efficacy of restrictive mitral annuloplasty (RMA) alone with that of RMA combined with SVR in patients with functional mitral regurgitation (MR).