Heima Sakaguchi

Impact of the Evolution of the Fontan Operation on Early and Late Mortality: A Single-Center Experience of 405 Patients Over 3 Decades

BACKGROUND Postoperative mortality has decreased in patients undergoing the Fontan operation, and the determinants of such mortality may also have changed significantly. METHODS We conducted a study intended to focus on clarifying the determinants of mortality in 405 consecutive patients who had undergone a Fontan operation (62 patients after an atriopulmonary connection, 105 after an intra-atrial rerouting, and 238 patients after an extracardiac rerouting) between 1979 and 2010. RESULTS The overall 1-year, 5-year, 10-year, and 15-year rates of survival were 87.1%, 84.6%, 83.4%, and 81.6%, respectively, and the type of procedure as well as heterotaxy syndrome, ventricular ejection fraction, and atrioventricular valve repair at the time of the Fontan operation were independent predictors of overall mortality (p < 0.05 for all). Heterotaxy syndrome and atrioventricular (AV) valve repair were independent predictors of early (less than 6 months postoperative) mortality and the type of procedure was an independent predictor of late (6 or more months postoperative) mortality (p < 0.05 to 0.01). In the era of intra-atrial rerouting, heterotaxy syndrome was the only independent predictor of total, early, and late mortality (p < 0.05 for all), whereas a low ejection fraction, AV valve repair, and repair of a total anomalous pulmonary vein connection, rather than heterotaxy syndrome, were independent predictors of total or early mortality or both (p < 0.05 for all) in the era of extracardiac rerouting. CONCLUSIONS Even in the modern era of extracardiac rerouting in the Fontan operation, a low ventricular ejection fraction, AV valve dysfunction, or a total anomalous pulmonary vein connection remain significant risk factors for mortality in patients with a single-ventricle physiology.

Changes in causes of sudden deaths by decade in patients with coronary arterial lesions due to Kawasaki disease

Over a 25-year period, we encountered 12 patients who died suddenly with coronary arterial lesions due to Kawasaki disease. We report their clinical course, and analyze the happenings of their deaths. Of the 12 patients, 10 were dead on arrival at hospital. Their age at death ranged from 13 months to 27 years, with a median of 16 years, and the interval from the onset of Kawasaki disease to death ranged from 2 months to 24 years. In 4 patients, death was found to be due to myocardial infarction, while in the remaining 8, it could not be determined. In 7 patients, coronary angiograms obtained less than 4 months after the acute onset of Kawasaki disease showed lesions bilaterally, most being giant aneurysms. Myocardial infarction had occurred in 6 patients prior to their death. In 1 patient of the late 1970s, who collapsed after running, cardiac sequels had not been suspected prior to autopsy. During the 1980s, 3 infants with bilateral giant aneurysms died within a year of the initial onset of Kawasaki disease, with acute myocardial infarction being the cause in 2 of them. In the late 1990s, and the 2000s, 5 patients died suddenly with left ventricular dysfunction, their ejection fractions being less than 40 percent more than 20 years after the initial onset of Kawasaki disease. Prior to their sudden deaths, they had had no cardiac events for many years, but had suffered previous myocardial infarctions. Multifocal premature ventricular contractions, and non-sustained ventricular tachycardia, are probable risk factors in such patients. Careful follow-up, checking for ventricular arrhythmia, is needed to prevent sudden death in patients suffering left ventricular dysfunction in the setting of Kawasaki disease.

Haemodynamic characteristics before and after the onset of protein losing enteropathy in patients after the Fontan operation

OBJECTIVES Determinant risk factors for developing protein losing enteropathy (PLE), including haemodynamics, remain unclear in patients after the Fontan operation. METHODS Our purpose was to characterize the serial PLE haemodynamics before and after the onset and to determine the risk factors based on the cardiac catheterization-based analysis. RESULTS Of 354 Fontan survivors who had undergone postoperative cardiac catheterizations, we experienced 26 PLE patients during the follow-up. Non-left ventricular morphology systemic ventricle, functional one-lung pulmonary circulation and an early postoperative high central venous pressure (CVP) were associated with the PLE onset and the high CVP (odds ratio (OR) = 1.19 per 1 mmHg, 95% confidence interval (CI) 1.04-1.37, especially ≥12 mmHg, OR = 3.09, 95% CI 1.25-7.64, P < 0.05 for both) and one-lung pulmonary circulation (OR = 10.0-10.5, P < 0.001) independently predicted the onset. At the time of the PLE onset, a Fontan route stenosis/obstruction, arrhythmias, ventricular dysfunction/heart failure and pulmonary arterio-venous fistulae were demonstrated in 10 (38%), 8 (31%), 4 (15%) and 3 (12%) patients, respectively. When compared with 56 excellent Fontan survivors, the high CVP, ventricular end-diastolic pressure, and pulmonary artery resistance, and the low arterial oxygen saturation, systemic artery pressure, and ventricular ejection fraction characterized the pre-PLE Fontan haemodynamics (P < 0.05-0.0001). However, the following intensive treatments reduced the CVP, systemic artery pressure and cardiac output (P < 0.05-0.01), resulting in haemodynamics no different from those of the excellent survivors, except for the low systemic pressure (P < 0.0001). CONCLUSIONS The pre-PLE haemodynamics was characterized by several impaired haemodynamics, while those after PLE only by a low systemic pressure. A high early postoperative CVP was the only haemodynamic predictor for a new onset of PLE. Strict selective criteria for the operation and strategies to eliminate CVP-raising factors are mandatory to prevent a new onset of PLE.

Comparison of prognostic variables in children and adults with Fontan circulation

BACKGROUND Non-cardiac complications, such as hepato-renal and metabolic problems, are emerging late after the Fontan operation due to its unique hemodynamics. Consequently, associations between clinical variables and postoperative outcome may change during the prolonged postoperative course. METHODS AND RESULTS To determine if child and adult Fontan patients differ in the impact of cardiac and non-cardiac variables on clinical outcome, we prospectively evaluated associations between hemodynamics, neurohumoral factors, exercise variables, hepato-renal function and metabolic variables and unscheduled hospitalization, including death in 167 consecutive child and 116 adult Fontan patients. When compared with child patients, the adult patients showed higher rates of medications, lower cardiac index, higher values of natriuretic peptides, greater renal dysfunction, more cholestatic livers, and more impaired responses to exercise (p<0.05-0.0001). During the follow-up of 3.7 ± 2.1 years, 64 clinical events (37 in adults), including 13 deaths, occurred. A high CVP and low arterial oxygen satutration strongly predicted the child events (p<0.001), whereas these prognostic parameters were marginal in the adults. Instead, renal dysfunction and metabolic abnormality predicted adult events (p<0.05). Neurohumoral activation, low albumin, hyponatremia, and impaired exercise variables equally predicted clinical events in child and adult Fontan patients. CONCLUSIONS Distinctive differences in predictive value of clinical variables exist between child and adult Fontan patients. In addition to cardiac issues, we should consider non-cardiac determinents of clinical outcome to maximize our efforts to improve prognosis for adult Fontan survivors.

Prognostic value of exercise variables in 335 patients after the Fontan operation: a 23-year single-center experience of cardiopulmonary exercise testing.

BACKGROUND The prognostic value of cardiopulmonary exercise testing (CPX) for mortality risk remains controversial in Fontan patients. PURPOSE Our goal of the present study was to clarify the prognostic value of major CPX variables and the factors determining exercise capacity in a large cohort of Fontan patients. METHODS Since 1990, heart rate (HR), oxygen uptake (VO2 ), and ventilatory equivalent for carbon dioxide production (VE/VCO2 ) at peak exercise were determined in 335 Fontan patients (18 ± 5 years old), and the CPX variables were compared with the clinical profile and events. RESULTS When compared with 209 controls, peak HR (148 ± 24 bpm), VO2 (27 ± 7 mL/kg/minute, [61 ± 15%]), and VE/VCO2 (40 ± 8 [117 ± 24%]) were markedly impaired in the Fontan patients (P < .0001). During a follow-up of 3.1 ± 2.7 years, 62 Fontan pathophysiological-associated events requiring unscheduled hospitalization (USH) occurred, and 24 patients died. All the CPX variables predicted the USH and mortality (P < .001-.0001). On multivariate analysis, in addition to use of diuretics (P = .0007) and low cardiac index (P = .0426), peak VO2 independently predicted the USH (hazard ratio: 0.95 per %, 95% confidence interval: 0.91-0.99, P = .014), while for mortality, multivariate analysis revealed that, in addition to heterotaxy syndrome (P = .0128) and year at first Fontan operation (P = .0532), peak VO2 independently predicted mortality (hazard ratio: 0.88 per %, 95% confidence interval: 0.76-0.98, P = .0217). CONCLUSION Fontan patients exhibit markedly impaired CPX variables, and all the major variables, especially peak VO2 , predicted the risk of both morbidity and mortality.

Long-term prognostic value of cardiac autonomic nervous activity in postoperative patients with congenital heart disease

BACKGROUND Abnormal cardiac autonomic nervous activity (CANA) is not uncommon in postoperative patients with congenital heart disease (CHD). METHODS AND RESULTS We attempted to clarify the prognostic value of the CANA variables in postoperative CHD patients and prospectively evaluated the CANA variables in 292 consecutive biventricular and 91 Fontan repair patients. The CANA variables included the heart rate variability, arterial baroreflex sensitivity (BRS), washout ratio of the myocardial metaiodobenzylguanidine scintigraphy, and plasma norepinephrine level. With a follow-up of 10 ± 2 years, 98 total events that required hospitalization, including 13 deaths and 48 unscheduled cardiac events (UCEs), occurred. In all the CHD patients, all the CANA indices predicted the total events and UCEs. Of those, the NE level (p=0.0004) and BRS (p=0.0373) predicted the mortality. In a multivariate analysis, the BRS was an independent CANA-predictor for the total events (p=0.007). In the biventricular patients, the plasma NE level, heart rate variability, and BRS predicted the total events and UCEs and the BRS was the only independent CANA-predictor for the total events (p=0.0329). In the Fontan patients, the plasma NE level was the only predictor for the UCEs (p=0.0242) and no other CANA variables were independent predictors of the total events or UCEs. CONCLUSIONS All CANA variables, especially the BRS, were useful predictors for future clinical events in biventricular CHD patients, whereas no CANA variables, except for the plasma NE level, predicted future clinical events in the Fontan patients.

Cardiac Resynchronization Therapy for Various Systemic Ventricular Morphologies in Patients With Congenital Heart Disease

BACKGROUND Cardiac resynchronization therapy (CRT) can result in functional improvement and reduced mortality in patients with medically refractory heart failure. Although CRT is reportedly effective in patients with congenital heart disease (CHD), it is still controversial in patients who have systemic right ventricle. METHODS AND RESULTS: Twenty CHD patients treated with CRT since 2006 were divided into 3 groups based on systemic ventricular (sysV) morphology (7 with left ventricle [sLV], 7 with right ventricle [sRV], and 6 with unbalanced 2 ventricles as a single-ventricular physiology [sBV]). The acute effects of CRT on hemodynamics and sysV function before device implantation was retrospectively evaluated and the chronic (≥6 months) effects of CRT on late outcomes was assessed. In our CHD populations, sysV volume index was reduced from 139±41 to 118±33 ml/m(2)(P=0.04) after CRT, and there was significant improvement in B-type natriuretic peptide levels (from 341±384 to 160±152 pg/ml, P=0.01) and New York Heart Association (NYHA) functional class (from 2.1±0.6 to 1.8±0.7, P=0.02) on a late outcome. The sRV group did not show a late sysV volume reduction despite significant QRS shortening, and an increase of sysV peak dP/dt in the acute study differed from that of other groups. CONCLUSIONS CRT improves late hemodynamic and functional status in sLV and sBV CHD patients with a dyssynchronized sysV. However, an acute CRT effect cannot guarantee long-term benefit in sRV patients.

Optimal pacing sites for cardiac resynchronization therapy for patients with a systemic right ventricle with or without a rudimentary left ventricle.

AIMS This study aims to assess the impact of pacing sites on the effectiveness of cardiac resynchronization therapy (CRT) in systemic right ventricle (sRV) patients with/without a rudimentary left ventricle (rLV). METHODS AND RESULTS We evaluated 13 procedures in 11 sRV patients with a wide QRS (>150 ms). Based on the digitalization results of ventriculography, long-axis dyssynchrony (LD) was defined as extremely delayed right ventricular (RV) outflow tract movement: ≥100 ms delay from the RV apical contraction, and short-axis dyssynchrony (SD) was defined as a paradoxical contraction between the rLV and sRV caused by a conduction delay between the two ventricles. During the follow-up period (2.1 ± 1.9 years), the response rates were 71% (5/7) and 33% (2/6) in the sRV patients with and without an rLV, respectively (P = ns). Following the CRT, the QRS duration remained similar between the responders and nonresponders. Among five responders with an rLV, the leads were placed in the longitudinal RV direction in two with LD, longitudinal RV direction with fusion of the intrinsic QRS in two with LD + SD, and laterally on opposite sides of both ventricles in one with SD. Among two responders without an rLV, the leads were placed in the longitudinal RV direction in those two with LD. CONCLUSIONS In sRV patients with LD with/without an rLV, the leads should be placed at furthest sites in the longitudinal RV direction. In patients with an rLV and SD, the leads should be placed laterally on opposite sides of both ventricles.

The incidence and characteristics of supraventricular tachycardia in left atrial isomerism: A high incidence of atrial fibrillation in young patients☆

BACKGROUND In left atrial isomerism (LAI), both atria show left atrial morphology. Although bradyarrhythmias are frequent and highly complex in LAI patients, previous studies have reported a low incidence of supraventricular tachycardia (SVT). METHODS To evaluate the incidence and characteristics of SVT in LAI, we retrospectively evaluated the clinical characteristics of SVTs in 83 patients with LAI (age at last follow-up, 15.3±10.5 years). RESULTS There were 27 SVTs in 19 patients (23%), including nine episodes of atrial fibrillation (AF) and eight non-reentrant SVTs. Sixteen of the 19 patients with SVT had histories of atriotomy, but the three patients with AF or non-reentrant tachycardia had no history of atriotomy. The rates of freedom from SVT were 66% and 59% at ages of 20 and 30 years, respectively; the corresponding rates for freedom from AF were 89% and 74%. In multivariate analysis, the predictors of SVT were age (OR, 1.14; 95% CI, 1.06-1.26; p=0.003) and sinus node dysfunction (SND) (OR, 3.88; 95% CI, 1.57-13.34; p=0.01). CONCLUSIONS In patients with LAI, SVTs are common, and AF and non-reentrant SVTs are the major type of SVTs. The incidence of AF was high in young patients with LAI. The lack of anatomical barriers in the atria that allow the formation of macro-reentrant circuits may account for the higher incidence of AF and non-reentrant SVT than macro-reentrant tachycardia. Moreover, the increasing prevalence of SND with age should contribute to a higher incidence of SVT.

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) Associated With Ryanodine Receptor (RyR2) Gene Mutations – Long-Term Prognosis After Initiation of Medical Treatment –

BACKGROUND The long-term prognosis of cardiac ryanodine receptor (RyR2) positive catecholaminergic polymorphic ventricular tachycardia (CPVT) patients after initiation of medical therapy has not been well investigated. This study aimed to assess the recurrence of fatal cardiac event after initiation of medical therapy inRyR2-positive CPVT patients. METHODSANDRESULTS Thirty-fourRyR2-positive CPVT patients with a history of cardiac events were enrolled. All patients had medical treatment initiated after the first symptom or diagnosis. Exercise stress tests (ESTs) were performed to evaluate the efficacy of the medical therapy. Even after the initiation of medical therapy, high-risk ventricular arrhythmias (VAs), including premature ventricular contraction couplets, bigeminy, and ventricular tachycardia, were still induced in the majority of patients (80.6%). During 7.4 years of follow-up after the diagnosis, 7 of the 34 (20.6%) patients developed fatal cardiac events. Among those 7 patients, 6 (85.7%) were not compliant with either exercise restriction or medication therapy at the time of the events. CONCLUSIONS Even after initiation of medical treatment, high-risk VAs were induced during EST in mostRyR2-positive CPVT patients. Most fatal recurrent cardiac events occurred in patients who were noncompliant with exercise restriction and/or medical therapy. Medical management including strict exercise restriction should be emphasized to prevent recurrent cardiac event in mostRyR2-positive CPVT patients. (Circ J 2016; 80: 1907-1915).