Alessandra Frigiola

Biventricular Response After Pulmonary Valve Replacement for Right Ventricular Outflow Tract Dysfunction Is Age a Predictor of Outcome

Background— The timing of pulmonary valve replacement (PVR) for free pulmonary incompetence in patients with congenital heart disease remains a dilemma for clinicians. We wanted to assess the determinants of improvement after PVR for pulmonary regurgitation over a wide range of patient ages and to use any identified predictors to compare clinical outcomes between patient groups. Methods and Results— Seventy-one patients (mean age 22±11 years; range, 8.5 to 64.9; 72% tetralogy of Fallot) underwent PVR for severe pulmonary regurgitation. New York Heart Association class improved after PVR (median of 2 to 1, P<0.0001). MRI and cardiopulmonary exercise testing were performed before and 1 year after intervention. After PVR, there was a significant reduction in right ventricular volumes (end diastolic volume 142±43 to 91±18, end systolic volume 73±33 to 43±14 mL/m2, P<0.0001), whereas left ventricular end diastolic volume increased (66±12 to 73±13 mL/m2, P<0.0001). Effective cardiac output significantly increased (right ventricular: 3.0±0.8 to 3.3±0.8 L/min, P=0.013 and left ventricular: 3.0±0.6 to 3.4±0.7 L/min, P<0.0001). On cardiopulmonary exercise testing, ventilatory response to carbon dioxide production at anaerobic threshold improved from 35.9±5.8 to 34.1±6.2 (P=0.008). Normalization of ventilatory response to carbon dioxide production was most likely to occur when PVR was performed at an age younger than 17.5 years (P=0.013). Conclusions— A relatively aggressive PVR policy (end diastolic volume <150 mL/m2) leads to normalization of right ventricular volumes, improvement in biventricular function, and submaximal exercise capacity. Normalization of ventilatory response to carbon dioxide production is most likely to occur when surgery is performed at an age ≤17.5 years. This is also associated with a better left ventricular filling and systolic function after surgery.

Pulmonary regurgitation is an important determinant of right ventricular contractile dysfunction in patients with surgically repaired tetralogy of fallot

Background—Evaluation of right ventricular (RV) function in patients with pulmonary regurgitation (PR) after tetralogy repair remains challenging because of abnormal RV loading conditions. Methods and Results—We examined 124 patients, aged 21±11.4 years, who had tetralogy repair at 3.7±3.5 years. By Doppler echocardiography, 33 patients had mild, 22 moderate, and 69 severe PR; 55 had significant tricuspid regurgitation (TR). Myocardial velocities, myocardial acceleration during isovolumic contraction (IVA), strain, and strain rate were measured at RV and LV base. Tricuspid valve annulus was measured in a 4-chamber view. QRS, QT, and JT intervals and their dispersions were measured from 12-lead electrocardiogram. IVA in the RV was lower in all patients compared with controls (0.8±0.4 versus 1.8±0.5, P<0.0001) and correlated with the severity of PR (r=−0.43, P<0.0001), whereas myocardial velocities, and strain/strain rate did not. LV IVA correlated with PR (r=−0.32, P<0.001) and with RV IVA (r=0.28, P<0.003). Patients with severe PR had a higher incidence of TR (r=0.69, P<0.0001) and lower RV IVA (1.0±0.4 versus 0.6±0.3, P<0.0001), a larger tricuspid valve ring diameter (P<0.0001), and prolonged electrical depolarization (P<0.001). Age at surgery or examination did not correlate with PR and with RV function assessed by IVA. In the RV, IVA correlated inversely with QRS duration (P<0.01). Conclusions—Although load-dependent myocardial velocities and strain are not influenced by the severity of PR and presence of significant TR, IVA demonstrates reduced contractile function in relation to the degree of PR and may be an early, sensitive index for selecting patients for valve replacement.

Variations in right ventricular outflow tract morphology following repair of congenital heart disease: Implications for percutaneous pulmonary valve implantation

OBJECTIVE Our aim was to identify sub-groups of right ventricular outflow tract morphology that would be suitable for percutaneous pulmonary valve implantation and to document their prevalence in our patient population. MATERIALS AND METHODS Eighty-three consecutive patients with right ventricular outflow tract dysfunction (5-41 years, 76% tetralogy of Fallot) referred to our center for cardiovascular magnetic resonance were studied. A morphological classification was created according to visual assessment of three-dimensional reconstructions and detailed measurement. Diagnosis, right ventricular outflow tract type, surgical history and treatment outcomes were documented. RESULTS Right ventricular outflow tract morphology was heterogeneous; nevertheless, 5 patterns were visually identified. Type I, a pyramidal morphology, was most prevalent (49%) and related to the presence of a transannular patch. Other types (II-V) were seen more commonly in patients with conduits. Two patients had unclassifiable morphology. Ninety-five percent of patients were assigned to the correct morphological classification by visual assessment alone. Percutaneous pulmonary valve implantation was performed successfully in 10 patients with Type II-V morphology and in 1 patient with unclassifiable morphology. Percutaneous implantation was not performed in patients with Type I morphology. Only right ventricular outflow tract diameters < 22 mm in diameter were suitable for the current device. CONCLUSIONS We have created a morphological classification of the RVOT in patients referred for assessment of RVOT dysfunction. Though only 13% of our patients underwent percutaneous implantation, > 50% of outflow tract morphologies may be suitable for this approach, in particular with the development of new devices appropriate for larger outflow.

Loss to specialist follow-up in congenital heart disease; out of sight, out of mind

Objective To evaluate the scale and clinical importance of loss to follow-up of past patients with serious congenital heart disease, using a common malformation as an example. To better understand the antecedents of loss to specialist follow-up and patients’ attitudes to returning. Design Cohort study using NHS number functionality. Content and thematic analysis of telephone interviews of subset contacted after loss to follow-up. Patients, intervention and setting Longitudinal follow-up of complete consecutive list of all 1085 UK patients with repair of tetralogy of Fallot from single institution 1964–2009. Main outcome measures Survival, freedom from late pulmonary valve replacement, loss to specialist follow-up, shortfall in late surgical revisions related to loss to follow-up. Patients’ narrative about loss to follow-up. Results 216 (24%) of patients known to be currently alive appear not to be registered with specialist clinics; some are seen in general cardiology clinics. Their median age is 32 years and median duration of loss to follow-up is 22 years; most had been lost before Adult Congenital services had been consolidated in their present form. 48% of the late deaths to date have occurred in patients not under specialist follow-up. None of those lost to specialist follow-up has had secondary pulmonary valve replacement while 188 patients under specialist care have. Patients lost to specialist follow-up who were contacted by telephone had no knowledge of its availability. Conclusions Loss to specialist follow-up, typically originating many years ago, impacts patient management.

Rescue surgery following percutaneous pulmonary valve implantation

OBJECTIVE Percutaneous pulmonary valve insertion (PPVI) is an evolving alternative to surgical pulmonary valve insertion. The aim of this study is to review the acute complications of PPVI requiring emergency rescue surgery. PATIENTS AND METHODS Between 09/2000 and 01/2007, 152 patients (pts), received a PPVI. Patients charts were reviewed in retrospect. RESULTS Emergency rescue surgery (ERS) took place in 6 pts (3.9%). Indications for ERS were: homograft rupture two pts, dislodgment of the stented valve in a dilated right ventricular outflow tract two pts, occlusion of the right pulmonary artery one pt and compression of the left main coronary artery one pt. Cardiopulmonary bypass was established through repeat sternotomy incision with femorofemoral cannulation in 2/6 pts. The stented valve was removed in five and replaced with a homograft in three and a valved conduit in two pts. One ruptured homograft was repaired leaving the stented valve in situ. All patients survived, one sustained mild neurological impairment. CONCLUSION Although some of the acute complications of PPVI were probably related to a learning curve (4 among the first 50 pts and 2 among the last 102 patients) the need for ERS is unlikely to be completely abolished. This experience highlights the importance of close collaboration between cardiologists and surgeons in these evolving technologies. Highly skilled and responsive surgical back up is necessary to support the introduction and to sustain institutional programmes such as PPVI.

Current approaches to pulmonary regurgitation

OBJECTIVE To evaluate the effects on ventricular function and volumes following right ventricular outflow tract reconstruction (RVOTR) with pulmonary homograft replacement (PVR) and percutaneous pulmonary valve implantation (PPVI) for predominant pulmonary regurgitation. This study was not intended to compare the two approaches. METHODS We prospectively examined 25 patients (mean age 21+/-13 years, 96% tetralogy of Fallot, 1/25 with conduit dysfunction) who had PVR with RVOTR for severe pulmonary regurgitation (PR), and 11 patients (mean age 20+/-9 years, 64% tetralogy of Fallot, 9/11 with conduit dysfunction) who underwent PPVI for predominant PR. Mean age at primary repair in both groups was 4.3+/-6.6 years. Magnetic resonance imaging was performed prior to, and 1 year following, interventions. RESULTS Before procedure, NYHA classification was similar in both groups 2.1+/-0.5. Following interventions, there was a significant reduction in RV volumes in both groups. In the surgical (PVR) group, RV end-diastolic volume (EDV) decreased from 151+/-49 to 97+/-32 ml/m(2) (p<0.0001) whereas end-systolic volume (ESV) decreased from 80+/-43 to 46+/-23 ml/m(2) (p<0.0001). In the PPVI group, RV EDV decreased from 106+/-27 to 89+/-25 ml/m(2) (p=0.002) and RV ESV from 49+/-20 to 40+/-16 ml/m(2) (p=0.034). Both groups had a significant improvement in RV (63+/-20 to 72+/-16 ml/beat, p=0.003 (PVR group), 53+/-14 to 67+/-16 ml/beat, p=0.030 (PPVI group)) and LV effective stroke volume (61+/-18 to 73+/-16 ml/beat, p=0.001 (PVR group); 59+/-24 to 75+/-16 ml/beat, p=0.009 (PPVI group)). CONCLUSIONS Following either PVR with RVOTR or PPVI, there was a significant reduction in RV volumes and an improvement in RV function. Importantly, in both groups, LV effective SV increased, and this may be the parameter to judge the benefit of the procedure. These results also support PPVI as an extra dimension in complex RVOT management.

Physiological and Phenotypic Characteristics of Late Survivors of Tetralogy of Fallot Repair Who Are Free From Pulmonary Valve Replacement

Background— Pulmonary valve replacement (PVR) after repair of tetralogy of Fallot is commonly required and is burdensome. Detailed anatomic and physiologic characteristics of survivors free from late PVR and with good exercise capacity are not well described in a literature focusing on the indications for PVR. Methods and Results— Survival and freedom from PVR were tracked in 1085 consecutive patients receiving standard tetralogy of Fallot repair in a single institution from 1964 to 2009. Of 152 total deaths, 100 occurred within the first postoperative year. Surviving patients between 10 and 50 years of age had an annual risk of death of 4 (confidence limit, 2.8–5.4) times that of normal contemporaries. To date, 189 patients have undergone secondary PVR at mean age of 20±13 years (36% of those alive at 40 years of age). A random sample of 50 survivors (age, 4–57 years) free from PVR underwent cardiovascular magnetic resonance, echocardiography, and exercise testing. These patients had mildly dilated right ventricles (right ventricular end-diastolic volume=101±26 mL/m2) with good systolic function (right ventricular ejection fraction=59±7%). Most had exercise capacity within normal range (z peak O2=−0.91±1.3; z E/ CO2=0.20±1.5). In patients >35 years of age with normal exercise capacity, there was mild residual right ventricular outflow tract obstruction (mean gradient, 24±13 mm Hg), pulmonary annulus diameters <0.5z, and unobstructed branch pulmonary arteries. Conclusions— An important proportion of patients require PVR late after tetralogy of Fallot repair. Patients surviving to 35 years of age without PVR and with a normal exercise capacity may have had a definitive primary repair; their right ventricular outflow tracts are characterized by mild residual obstruction and pulmonary annulus diameter <0.5z.

Percutaneous pulmonary valve replacement

Percutaneous pulmonary valve implantation helps in prolonging the lifespan of surgically placed right ventricle-to-pulmonary artery (RV-PA) conduits, and represents a less invasive alternative to repeat open-heart surgery. The clinical indications for treatment match those of surgery. As far as the suitability is concerned, the current ideal substrate is a degenerated RV-PA conduit, because of the presence of a certain degree of calcification that offers a safe anchoring point. So far, patients have been treated with low morbidity and mortality that were further improved with increasing experience. After percutaneous pulmonary valve implantation, patients experience a subjective improvement, mirrored by an objective increase of measured exercise capacity parameters and by reduced RV-PA gradient, regurgitant fraction, and RV volumes. New developments in the experimental field should result in an extension of indications in the future.

Lifetime costs and outcomes of repair of Tetralogy of Fallot compared to natural progression of the disease: Great Ormond Street Hospital cohort.

Background Tetralogy of Fallot is a congenital heart disease that requires surgical repair without which survival through childhood is extremely rare. The aim of this paper is to use data from the mandatory follow-up of patients with Tetralogy of Fallot to model the health-related costs and outcomes over the first 55-years of life. Method A decision analytical model was developed to establish costs and outcomes for patients up to 55 years after diagnosis and first repair of Tetralogy of Fallot compared to natural progression. Data from Adult Congenital Heart Disease (ACHD) centres that follow up Tetralogy of Fallot patients and Great Ormond Street Hospital (GOSH), London, United Kingdom (UK) medical records was used to establish the cost and effectiveness of current interventions. Data from a Czech cohort was used for the natural, no intervention condition. Results The average cost per patient of a repair for Tetralogy of Fallot was £26,938 (SE = £4,140). The full life time cost per patient, with no discount rate, was £65,310 (95% CI £64,981–£65,729); £56,559 discounted (95% CI £56,159–£56,960). Patients with a repair had an average of 35 Quality Adjusted Life Years (QALYs) per patient over 55 years undiscounted and 20.16 QALYs discounted. If the disorder was left to take its natural course, patients on average had a total of 3 QALYs per patient with no discount rate and 2.30 QALYs discounted. Conclusion A model has been developed that provides an estimate of the value for money of an expensive repair of a congenital heart disease. The model could be used to test the cost-effectiveness of making amendments to the care pathway.

Exercise capacity, quality of life, and resilience after repair of tetralogy of Fallot: a cross-sectional study of patients operated between 1964 and 2009

INTRODUCTION Patients with repaired tetralogy of Fallot have good long-term survival but less is known about the subjectively assessed quality of life or objectively measured functional status of those who have not required subsequent pulmonary valve replacement. We assessed these parameters in a group of children and adults free from pulmonary valve replacement after tetralogy of Fallot repair. METHODS AND RESULTS A random sample of 50 subjects--16 children and 34 adults, aged 4.1-56.7 years---who had undergone tetralogy of Fallot repair and were free from subsequent pulmonary valve replacement underwent cardiopulmonary exercise testing and completed standardised questionnaires assessing health-related quality of life and resilience. Patients were generally asymptomatic (median New York Heart Association class = I). Exercise capacity was within two standard deviations of normal for most children and adults (mean z VO2max: 0.20 ± 1.5; mean z VE/VCO2: -0.9 ± 1.3). Children reported a total health-related quality of life score similar to healthy norms (78 ± 10 versus 84 ± 1, p = 0.73). Adult survivors also reported quality of life scores comparable to healthy norms. Resilience was highly correlated with all domains of health-related quality of life (r = 0.713, p < 0.0001). CONCLUSIONS Patients who have undergone tetralogy of Fallot repair in childhood and have not required pulmonary valve replacement have a good long-term health-related quality of life. The finding that patients with greater resilience had better health-related quality of life suggests that it may be beneficial to implement interventions to foster resilience.