Ventricular size and function assessed by cardiac MRI predict major adverse clinical outcomes late after tetralogy of Fallot repair.

BACKGROUND: Factors associated with impaired clinical status in a cross-sectional study of patients with repaired tetralogy of Fallot (TOF) have been reported previously. OBJECTIVES: To determine independent predictors of major adverse clinical outcomes late after TOF repair in the same cohort during follow-up evaluated by cardiac magnetic resonance (CMR). METHODS: Clinical status at latest follow-up was ascertained in 88 patients (median time from TOF repair to baseline evaluation 20.7 years; median follow-up from baseline evaluation to most recent follow-up 4.2 years). Major adverse outcomes included (a) death; (b) sustained ventricular tachycardia; and (c) increase in NYHA class to grade III or IV. RESULTS: 22 major adverse outcomes occurred in 18 patients (20.5%): death in 4, sustained ventricular tachycardia in 8, and increase in NYHA class in 10. Multivariate analysis identified right ventricular (RV) end-diastolic volume Z >or=7 (odds ratio (OR) = 4.55, 95% confidence interval (CI) 1.10 to 18.8, p = 0.037) and left ventricular (LV) ejection fraction <55% (OR = 8.05, 95% CI 2.14 to 30.2, p = 0.002) as independent predictors of outcome with an area under the receiver operator characteristic curve of 0.850. LV ejection fraction could be replaced by RV ejection fraction <45% in the multivariate model. QRS duration >or=180 ms also predicted major adverse events but correlated with RV size. CONCLUSIONS: In this cohort, severe RV dilatation and either LV or RV dysfunction assessed by CMR predicted major adverse clinical events. This information may guide risk stratification and therapeutic interventions.

Vasoresponsiveness of sarcoidosis-associated pulmonary hypertension.

OBJECTIVE: To assess short-term and long-term responses to treatment with pulmonary vasodilators in patients with sarcoidosis-related pulmonary hypertension. METHODS: A prospective, observational study was performed on eight patients with moderate-to-severe sarcoidosis-related pulmonary hypertension. Patients underwent a short-term vasodilator trial, using inhaled nitric oxide (iNO), IV epoprostenol, and/or oral calcium-channel blockers. A favorable short-term response was considered a > or = 20% decrease in pulmonary vascular resistance (PVR). Five patients received long-term treatment with iNO (with one patient receiving epoprostenol in addition) and underwent follow-up hemodynamic and/or 6-min walk testing. Two patients received long-term treatment with calcium-channel blockers. RESULTS: Baseline (+/- SE) mean pulmonary artery pressure (mPAP) was 55 +/- 4 mm Hg and PVR was 896 +/- 200 dyne.s.cm(-5). A favorable short-term response was seen in seven of eight patients receiving iNO, four of six patients receiving epoprostenol, and two of five patients receiving calcium-channel blockers. With iNO, PVR decreased 31 +/- 5% (p = 0.006) and mPAP decreased 18 +/- 4% (p = 0.003); with epoprostenol, PVR decreased 25 +/- 6% (p = 0.016) and mPAP decreased 6 +/- 2% (p = not significant). Decreased systemic vascular resistance was the only significant response to treatment with calcium-channel blockers. Follow-up 6-min walk test results improved in all five patients receiving long-term treatment with iNO. Follow-up hemodynamic responses in three patients showed preserved vasoresponsiveness. These three patients subsequently died, as did the two patients receiving calcium-channel blockers. The two remaining patients continue to receive iNO. CONCLUSION: In the short term, pulmonary hypertension in patients with sarcoidosis is responsive to treatment with pulmonary vasodilators; these patients may benefit from long-term iNO therapy.

Percutaneous coronary intervention and subsequent endovascular beta-radiation brachytherapy in a 14-year-old with repaired anomalous left coronary artery from pulmonary artery.

Anomalous origin of the left coronary artery from pulmonary artery (ALCAPA) is a rare congenital anomaly. Re-establishment of the dual coronary system is the standard treatment, although the long-term outcome after surgical repair is not well defined. We report a case in which coronary stenting was performed to treat left anterior descending artery lesions eight months after surgical repair of ALCAPA. The patient then developed rapid in-stent restenosis within three months, which was successfully treated by rotational atherectomy, balloon angioplasty, and catheter-based beta-radiation brachytherapy. Follow-up angiograms after three and six months showed no recurrent in-stent restenosis. This represents the first report of coronary stenting in the setting of ALCAPA, and the first report of catheter-based intracoronary radiation therapy in a pediatric patient.

Multi atrial maco-re-entry circuits in adults with repaired congenital heart disease: entrainment mapping combined with three-dimensional electroanatomic mapping.

OBJECTIVES: We sought to characterize re-entry circuits causing intra-atrial re-entrant tachycardias (IARTs) late after the repair of congenital heart disease (CHD) and to define an approach for mapping and ablation, combining anatomy, activation sequence data and entrainment mapping. BACKGROUND: The development of IARTs after repair of CHD is difficult to manage and ablate due to complex anatomy, variable re-entry circuit locations and the frequent co-existence of multiple circuits. METHODS: Forty-seven re-entry circuits were mapped in 20 patients with recurrent IARTs refractory to medical therapy. In the first group (n = 7), ablation was guided by entrainment mapping. In the second group (n = 13), entrainment mapping was combined with a three-dimensional electroanatomic mapping system to precisely localize the scar-related boundaries of re-entry circuits and to reconstruct the activation pattern. RESULTS: Three types of right atrial macro-re-entrant circuits were identified: those related to a lateral right atriotomy scar (19 IARTs), the Eustachian isthmus (18 IARTs) or an atrial septal patch (8 IARTs). Two IARTs originated in the left atrium. Radiofrequency (RF) lesions were applied to transect critical isthmuses in the right atrium. In three patients, the combined mapping approach identified a narrow isthmuses in the lateral atrium, where the first RF lesion interrupted the circuit; the remaining circuits were interrupted by a series of RF lesions across a broader path. Overall, 38 (81%) of 47 IARTs were successfully ablated. During follow-up ranging from 3 to 46 months, 16 (80%) of 20 patients remained free of recurrence. Success was similar in the first 7 (group 1) and last 13 patients (group 2), but fluoroscopy time decreased from 60 +/- 30 to 24 +/- 9 min/procedure, probably related to the increasing experience and ability to monitor catheter position non-fluoroscopically. CONCLUSIONS: Entrainment mapping combined with three-dimensional electroanatomic mapping allows delineation of complex re-entry circuits and critical isthmuses as targets for ablation. Radiofrequency catheter ablation is a reasonable option for treatment of IARTs related to repair of CHD.

Balloon pulmonary angioplasty for treatment of chronic thromboembolic pulmonary hypertension.

BACKGROUND: Although pulmonary thromboendarterectomy is increasingly successful for the definitive treatment of chronic thromboembolic pulmonary hypertension (CTEPH), not all patients have surgically accessible disease. Others are poor surgical candidates because of comorbid illness. Therefore, for selected patients, we defined and implemented an alternative interventional strategy of balloon pulmonary angioplasty (BPA). METHODS AND RESULTS: Eighteen patients (mean age, 51.8 years; range, 14 to 75 years) with CTEPH underwent BPA; they averaged 2.6 procedures (range, 1 to 5) and 6 dilations (range, 1 to 12). Selection of pulmonary artery segments for dilation required (1) complete occlusion, (2) filling defects, or (3) signs of intravascular webs. After an average of 36 months of follow-up (range, 0.5 to 66 months), the average New York Heart Association class improved from 3.3 to 1.8 (P:<0.001), and 6-minute walking distances increased from 209 to 497 yards (P:<0.0001). Pulmonary artery mean pressures decreased from 43.0+/-12.1 to 33. 7+/-10.2 mm Hg (P:=0.007). Eleven patients developed reperfusion pulmonary edema; 3 required mechanical ventilation. CONCLUSIONS: BPA reduces pulmonary artery hypertension in patients with CTEPH and is associated with long-term improvement in New York Heart Association class and 6-minute walking distances. BPA is a promising interventional technique that warrants randomized comparison with medical therapy in CTEPH patients who are not surgical candidates.

Closure of atrial septal defects in adult patients: justification of the "tipping point".

The "tipping point," favoring closure of hemodynamically significant atrial septal defects (ASDs) in the adult, has occurred and is supported by strong clinical data, especially in patients who present with symptoms. Echocardiographic evidence of right ventricular volume overload as a correlate of significant left-to-right intracardiac shunting remains a prerequisite to determine need for closure, even in patients with child-bearing potential. No patient appears too old to achieve benefit from closure of such defects. Modern therapeutics for pulmonary vascular disease may allow extension of these techniques to an increasingly threatened population, with care best coordinated and offered in appropriate centers of expertise.

Closure of patent foramen ovale for paradoxical emboli: intermediate-term risk of recurrent neurological events following transcatheter device placement.

OBJECTIVES: We report the largest and the longest follow-up to date of patients who underwent transcatheter patent foramen ovale (PFO) closure for paradoxical embolism. BACKGROUND: Closure of a PFO has been proposed as an alternative to anticoagulation in patients with presumed paradoxical emboli. METHODS: Data were collected for patients following PFO closure with the Clamshell, CardioSEAL or Buttoned Devices at two institutions. RESULTS: There were 63 patients (46 +/- 18 years) with a follow-up of 2.6 +/- 2.4 years. Fifty-four (86%) had effective closure of the foramen ovale (trivial or no residual shunt by echocardiography) while seven (11%) had mild and two (3%) had moderate residual shunting. There were four deaths (leukemia, pulmonary embolism, sepsis following a hip fracture and lung cancer). There were four recurrent embolic neurological events following device placement: one stroke and three transient events. The stroke occurred in a 56-year-old patient six months following device placement. A follow-up transesophageal echocardiogram showed a well seated device without residual shunting. Two of the four events were associated with suboptimal device performance (one patient had a significant residual shunt and a second patient had a "friction lesion" in the left atrial wall associated with a displaced fractured device arm). The risk of recurrent stroke or transient neurological event following device placement was 3.2% per year for all patients. CONCLUSION: Transcatheter closure of PFO is an alternative therapy for paradoxical emboli in selected patients. Improved device performance may reduce the risk of recurrent neurological events. Further studies are needed to identify patients most likely to benefit from this intervention.

Accuracy of MRI evaluation of pulmonary blood supply in patients with complex pulmonary stenosis or atresia.

Detailed imaging of pulmonary artery (PA) anatomy and significant aorto-pulmonary collaterals (APCs) is crucial for surgical planning and follow-up in patients with complex congenital heart disease (CHD) and pulmonary stenosis or atresia. Because examination by echocardiography is often technically limited and catheterization is invasive, this study evaluated the diagnostic accuracy of magnetic resonance imaging (MRI) as an alternate non-invasive tool. Thirteen patients (median age 28 years, range: 1-44 years) underwent both cardiac catheterization and MRI within a median of two months (range 0.1-8 months). Diagnoses included tetralogy of Fallot (TOF) with pulmonary atresia (n = 8), TOF with pulmonary stenosis (n = 2), single left ventricle with pulmonary stenosis (n = 2), and complex heterotaxy with pulmonary stenosis (n = 1). The MRI sequences used in this study were ECG-gated spin echo and gradient echo sequences acquired in multiple planes. Compared to catheterization, MRI had 100% sensitivity and specificity for the diagnosis of main PA (n = 6) and branch PA (n = 13) hypoplasia or stenosis, as well as discontinuous (n = 4) or absent (n = 10) branch PAs. There was complete agreement between catheterization and MRI identification of significant APCs (n = 18). Main PA atresia was noted by MRI in four patients but was not definitively seen by catheterization in any. MRI but not catheterization precisely defined the distance between discontinuous PAs and their relationship to other mediastinal structures. In conclusion, cardiac MRI is a reliable non-invasive imaging modality to define PA and APC anatomy in patients with complex pulmonary stenosis or atresia.

Inhaled nitric oxide therapy in pregnancy complicated by pulmonary hypertension.

The use of nitric oxide as an agent to reduce pulmonary artery pressure in a pregnancy complicated by pulmonary hypertension is reported for the first time. This therapy can reduce pulmonary vascular resistance and therefore potentially enable the right ventricle to better compensate for the physiologic changes of pregnancy.

In vivo evaluation of Fontan pathway flow dynamics by multidimensional phase-velocity magnetic resonance imaging.

BACKGROUND: Hemodynamic efficiency of Fontan circulation is believed to be a major determinant of outcome. Prior research on flow dynamics in different modifications of Fontan circulation used in vitro models and computer-based simulation. This study was designed to compare in vivo flow dynamics in the systemic venous pathway between patients with atriopulmonary anastomosis (APA) and those with total cavopulmonary connection (TCPC). METHODS AND RESULTS: Multidimensional phase-velocity magnetic resonance imaging (PV-MRI) studies were performed on 10 patients who had undergone a modified Fontan operation (5 with TCPC and 5 with APA) and were free of symptoms. The groups were comparable in terms of age and body surface area. The interval since surgery was longer for APA than for TCPC subjects. In each subject, the phase-velocity data sets were used to generate dynamic velocity-vector maps and to calculate quantitative flow indices describing the 3-dimensional blood-flow patterns throughout the cardiac cycle at the widest diameter of the Fontan pathway. Mean flow rate was comparable between groups. Velocity-vector maps showed areas of flow reversal, flow stagnation, and circular flow within APA but not TCPC pathways. Analysis of quantitative flow indices showed that compared with the APA group, flow velocities in the TCPC patients were significantly higher (mean velocity, 14+/-6 cm/s versus 5+/-3 cm/s; P=0.02), less variable (coefficient of variation, 19+/-2% versus 37+/-3.5%; P<0.0001), and more unidirectional (degree of unidirectionality, 89+/-7% versus 71+/-12%; P=0.03). APA pathways were significantly more dilated than were TCPC pathways (P<0.01) and showed a trend toward larger diameter with increased interval since surgery (R2=0.6, P=0.09). Fontan pathway dilatation correlated with flow velocity variability (R2=0.57, P=0.01) and inversely with flow unidirectionality (R2=0.75, P=0.001). CONCLUSIONS: Blood flow patterns are more organized and uniform in TCPC than in APA pathways and are significantly influenced by pathway diameter. We speculate that TCPC may result in a more hemodynamically efficient circulation than APA because of differences in pathway dimension and uniformity.

Transcatheter management of ventricular septal rupture after myocardial infarction.

Despite improvements in surgical management of ventricular septal rupture (VSR) after myocardial infarction (MI), perioperative risk may be excessive for particular patients. Our experience with transcatheter closure of congenital ventricular septal defects led to our transcatheter attempts to close VSR after MI in patients without prior surgical repair who were thought to have prohibitive surgical risk (7), or similarly ill patients who had residual shunting after attempted surgical VSR closure (11). Of the 11 patients with postoperative residual patch-margin defects, survival (median 54 months) has not been limited by procedural success in any. Of the 7 patients without prior surgical repair, survival past hospitalization or to the present occurred in 3 patients, all of whom presented months after initial VSR. All survivors are in NYHA class II. Our experience suggests that optimal management of patients with post MI-VSR requires surgical-medical collaboration that extends surgical success to highest risk patients via catheter-based therapeutics.

Isolated peripheral pulmonary artery stenoses in the adult.

BACKGROUND: Isolated peripheral pulmonary artery stenosis (PPS) in the adult is rare and frequently unsuspected. We review in this article our experience with 12 adult patients with isolated PPS, half of whom had been previously diagnosed with chronic pulmonary thromboembolic disease. METHODS AND RESULTS: The presentation, evolution, and management of 12 adults with isolated PPS, 17 to 51 years of age (mean, 36.2 +/- 9.7 years), were evaluated. Presenting symptoms were dyspnea and fatigue. Three patients had New York Heart Association (NYHA) functional class III or greater. Lung perfusion scans revealed multiple segmental abnormalities in flow distribution in all patients. Oxygen desaturation at rest was present in 4 patients. At catheterization, right ventricular (RV) pressure was suprasystemic in 2 patients, systemic in 1, and more than half-systemic in 7. All had multiple bilateral non-uniform stenoses in segmental and subsegmental arteries. Balloon pulmonary angioplasty (BPA) to decrease RV hypertension and improve pulmonary flow distribution was performed in 11 patients. After BPA, vessel diameter increased > 50% in 10 patients, distal pulmonary artery pressure increased > or = 30% in 6, and RV pressure decreased > 30% in 5. One patient died shortly after BPA as a result of pulmonary hemorrhage. Immediate procedural success was achieved in 9 of 11 patients. At a mean follow-up period of 52 +/- 32 months, 7 patients had sustained symptomatic improvement (NYHA class I-II). CONCLUSIONS: We describe a severe syndrome of isolated PPS in the adult that mimics chronic pulmonary thromboembolic disease. Pulmonary hemodynamics and angiography are required for definitive diagnosis. BPA may offer these patients successful short-term reduction in RV hypertension and alleviation of symptomatology.

Role of nitric oxide in the local regulation of pulmonary vascular resistance in humans.

BACKGROUND: Endothelium-derived nitric oxide (NO) may be an important mediator of vascular resistance in the pulmonary circulation. We tested the hypotheses that in conscious adults the endothelium, through NO production, is important in maintaining basal pulmonary vascular resistance and that it can increase NO production further in response to receptor-mediated stimulation, leading to further vasodilation. METHODS AND RESULTS: Pulmonary arterial resistance vessel function was studied within the distribution of a segmental lower lobe pulmonary artery in eight conscious adults 37 to 76 years old who were undergoing cardiac catheterization. Segmental blood flow was determined with use of a Doppler-tip guide wire and quantitative angiography. Drugs were administered locally within the segmental artery through an infusion catheter. NG-Monomethyl-L-arginine (L-NMMA) was used as a specific inhibitor of NO production, whereas acetylcholine (ACh) was used to test receptor-mediated vasodilation. To demonstrate that vasodilation to ACh was NO dependent, ACh response was tested alone, in the presence of L-NMMA, and in the presence of a control constrictor phenylephrine. Basal pulmonary vascular resistance was NO dependent because L-NMMA infusion resulted in a dose-dependent decrease in local flow velocity (P < .005), with flow decreasing 33% at the highest dose of L-NMMA. ACh infusion resulted in a dose-dependent increase in flow velocity (P = .001). The ACh response was at least in part NO dependent because it was diminished by the presence of L-NMMA (P < .05). The effect of L-NMMA on the ACh response was not due to nonspecific preconstriction because L-NMMA diminished the ACh response significantly more than did the endothelium-independent constrictor phenylephrine (P < .05) despite comparable preconstriction. CONCLUSIONS: In healthy conscious adults, (1) normal basal pulmonary resistance is maintained in part by continuous local production of NO and (2) the local NO production is responsive to receptor-mediated stimulation, leading to further vasodilation, and can be tested with ACh.

Orthodeoxia-platypnea due to intracardiac shunting--relief with transcatheter double umbrella closure.

The safety and efficacy of transcatheter clamshell occlusion of patent foramen ovale for relief of severe arterial desaturation and dyspnea in the upright position due to intracardiac shunting were examined in eight patients with excessive risk of surgical patent foramen ovale closure. All patients had successful reduction of intracardiac shunting with an immediate rise in oxygen saturation > or = 95% by implantation of a clamshell device on the atrial septum. Despite two early incidents of device embolization, retrieval and immediate re-implantation, and one patient with nonsustained atrial and ventricular arrhythmias, there were no adverse clinical sequelae. In follow-up evaluation transcatheter clamshell closure of patent foramen ovale has provided persistent relief from shunt-related arterial desaturation and symptomatology in all living patients.

Coronary artery abnormalities detected at cardiac catheterization following the arterial switch operation for transposition of the great arteries.

Because the arterial switch operation has become the routine surgical approach for transposition of the great arteries, there is increasing awareness of adverse sequelae in some survivors. For the arterial switch to be considered the procedure of choice for transposition of the great arteries, long-term patency and normal function of the translocated coronary arteries must be achieved. We reviewed the cineangiograms and hemodynamic data in 366 patients who underwent postoperative catheterization after arterial switch operation. Of these, 13 patients (3%) had previously unsuspected coronary abnormalities diagnosed angiographically. No patient had noninvasive evidence of resting systolic dysfunction. Findings included left main coronary artery stenosis (n = 3) or occlusion (n = 2), anterior descending coronary artery stenosis (n = 1) or occlusion (n = 2), right coronary artery stenosis (n = 1) or occlusion (n = 1), and small coronary artery fistulas (n = 3). One patient died suddenly 3.3 years after surgery, 1 patient is lost to follow-up, and the remaining 10 patients are alive and asymptomatic up to 11 years after surgery.

Balloon aortic valvuloplasty in the young adult with congenital aortic stenosis.

Although balloon aortic valvuloplasty (BAV) is effective in the acute management of valvar aortic stenosis (AS), sustained benefit of this technique has been shown to vary in differing age groups. The role of BAV in the young adult with congenital, nondegenerative AS is poorly defined. The catheterization results and follow-up echocardiographic data were reviewed for all patients (n = 18) between the ages of 17 and 40 years (mean 23 +/- 7) undergoing BAV at our institution between March 1986 and January 1992. Peak-to-peak systolic ejection gradient was reduced by 55%, from 85 +/- 29 to 38 +/- 17 mm Hg (p < 0.001). Aortic valve area increased from 0.9 +/- 0.2 to 1.1 +/- 0.3 cm2 (p = 0.003). Results of dilation were inadequate in 2 patients. There were no deaths, myocardial infarction, or embolic events. The 16 "effectively" dilated patients were followed with serial echocardiography for a period of 1 to 82 months, demonstrating persistent gradient relief in most patients (maximal instantaneous gradient at follow-up, 55 +/- 17 vs 79 +/- 22 mm Hg before dilation, p < 0.001). Aortic valve replacements were performed in 5 patients, 2 with unsuccessful initial dilations. At the time of the most recent echocardiogram, 8 of 16 patients remained "incident free," with no subsequent catheterization or surgical interventions, a maximal instantaneous gradient of < or = 55 mm Hg, no more than moderate aortic regurgitation, and preserved ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)

Interventional catheter procedures used in congenital heart disease.

Many of the transcatheter devices described in this article remain investigational in the United States. Currently, we consider the applications of these techniques as either (1) procedures of choice (for closures of patent ductus arteriosus, balloon dilation or stent implantation for peripheral pulmonary stenoses, balloon dilation of recurrent or persistent aortic coarctation, balloon pulmonary valvotomy, closure of congenital muscular or postoperative residual ventricular septal defects, closure of patent foramen ovale in the setting of cyanosis, balloon aortic valvotomy, fenestration closures, coil embolization of thoracic collateral vessels); (2) effective alternatives to surgical therapy (closures of atrial septal defects of the secundum type, balloon dilation of native aortic coarctation, stent implantation for conduit or baffle obstruction, device emobolization of paravalvular leaks or coronary artery fistulas); or (3) treatments with unproven effect (closure of acute postmyocardial infarction ventricular septal defects, closure of patent foramen ovale for idiopathic stroke, stent implantation for pulmonary venous stenosis) (Table 1). Patients with congenital heart disease often undergo multiple catheterizations and surgical therapies, each with its own complications and sequelae. Clinical trials of catheter-based technologies for patients with congenital heart disease have consisted of uncontrolled case series with a lack of standardized follow-up. Additional prospective large-scale clinical trials of these therapies seem necessary before their widespread acceptance.