Radiofrequency catheter ablation of persistent atrial fibrillation by pulmonary vein isolation with or without left atrial posterior wall isolation: long-term outcomes of the CAPLA trial.

BACKGROUND AND AIMS: Posterior wall isolation (PWI) is commonly incorporated into catheter ablation (CA) strategies for persistent atrial fibrillation (AF) in an attempt to improve outcomes. In the CAPLA randomized study, adjunctive PWI did not improve freedom from atrial arrhythmia at 12 months compared with pulmonary vein isolation (PVI) alone. Whether additional PWI reduces arrhythmia recurrence over the longer term remains unknown. METHODS: In this multicenter, international, randomized study patients with persistent AF undergoing index CA using radiofrequency (RF) were randomized to PVI+PWI versus PVI alone. Patients underwent regular follow-up including rhythm monitoring for a minimum of 3 years post CA. AF burden at 3 years post-ablation was evaluated with either 28-day continuous ambulatory ECG monitoring, twice daily single-lead ECG or from cardiac implanted device. Evaluated endpoints included freedom from any documented atrial arrhythmia recurrence after a single procedure, AF burden, need for redo catheter ablation, rhythm at last clinical follow-up, healthcare utilisation metrics and AF-related quality of life. RESULTS: 333 of 338 (98.5%) patients (mean age 64.3±9.4 years, 23% female) completed 3-year follow-up, with 169 patients randomized to PVI+PWI and 164 patients to PVI alone. At a median of 3.62 years post-index ablation, freedom from recurrent atrial arrhythmia occurred in 59 patients (35.5%) randomized to PVI+PWI vs 68 patients (42.1%) randomized to PVI alone (HR 1.15, 95% CI 0.88-1.51, p=0.55). Median time to recurrent atrial arrhythmia was 0.53 years (IQR 0.34-1.01 years). Redo ablation was performed in 54 patients (32.0%) in the PVI+PWI group vs 49 patients (29.9%, p=0.68) in the PVI alone group. Pulmonary vein reconnection was present in 54.5% (mean number of reconnected PVs 2.2±0.9) and posterior wall reconnection in 75%. Median AF burden at 3 years was 0% in both groups (IQR 0-0.85% PVI+PWI vs 0-1.43% PVI alone, p=0.49). Sinus rhythm at final clinical follow-up was present in 85.1% with PVI+PWI vs 87.1% with PVI alone (p=0.60). Mean AF Effect On Quality-Of-Life (AFEQT) score at 3 years post-ablation was 88.0±14.8 with PVI+PWI vs 88.9±15.4 with PVI alone (p=0.63). CONCLUSIONS: In patients with persistent AF, the addition of PWI to PVI alone at index RF catheter ablation did not significantly improve freedom from atrial arrhythmia recurrence at long-term follow-up. Median AF burden remains low and AF quality of life high at 3 years with either ablation strategy.

Isolated cleft mitral valve with severe regurgitation resulting in a left inferior pulmonary vein varix diagnosed from cardiovascular magnetic resonance imaging.

Isolated cleft mitral valve (ICMV) is a rare entity not known to be related to pulmonary atresia with ventricular septal defect (PA-VSD). This report describes the use of cardiovascular magnetic resonance (CMR) imaging to diagnose ICMV in a patient with repaired PA-VSD who presented with incidental severe mitral regurgitation (MR) on follow-up echocardiography. An associated pulmonary varix secondary to the severe MR also was shown by CMR.

Successful catheter ablation of incessant atrial tachycardia in pregnancy using three-dimensional electroanatomical mapping with minimal radiation.

Arrhythmias during pregnancy are not an infrequent problem and present a difficult therapeutic challenge to physicians. Anti-arrhythmic medication is used with some trepidation given concerns for the unborn foetus. Catheter ablation is typically avoided due to concerns regarding foetal exposure to radiation and delayed until the post-partum period. With the availability of three-dimensional mapping systems, catheter ablation may be performed with minimal radiation. We report a pregnant woman who underwent successful ablation of focal atrial tachycardia using three-dimensional electroanatomical mapping with minimal radiation exposure.

Expression and coexpression of Trk receptors in subpopulations of adult primary sensory neurons projecting to identified peripheral targets.

To determine whether neurotrophins act on functionally distinct populations of adult sensory neurons, the distributions of mRNAs for TrkA and tyrosine kinase-containing isoforms of TrkB and TrkC were determined in rat DRG neurons projecting to different peripheral targets. Whereas trkA was expressed by a very high percentage of visceral afferents, trkC was expressed frequently only in muscle afferents. Among cutaneous afferents, the size distributions for trkA- and trkC-positive cells showed little overlap. The percentages and size distributions of cells labeled for the trks argue strongly that almost all trkB-expressing cells must also express trkA or trkC. These results indicate that NGF and NT-3 act on functionally distinct populations of adult sensory neurons and suggest that a sizeable number of small DRG neurons may not respond to neurotrophins via a known Trk in the adult rat.

Annulus paradoxus: transmitral flow velocity to mitral annular velocity ratio is inversely proportional to pulmonary capillary wedge pressure in patients with constrictive pericarditis.

BACKGROUND: The early diastolic velocity of the mitral annulus (E') is reduced in patients with diastolic dysfunction and increased filling pressures. Because transmitral inflow early velocity (E) increases progressively with higher filling pressures, E/E' has been shown to have a strong positive relationship with pulmonary capillary wedge pressure (PCWP) and left ventricular end-diastolic pressure. However, previous studies have primarily involved patients without a pericardial abnormality. In constrictive pericarditis (CP), E' is not reduced, despite increased filling pressures. This study evaluated the relationship between E/E' and PCWP in patients with CP. METHODS AND RESULTS: We studied 10 patients (8 men; mean age, 64+/-7 years) with surgically confirmed CP. Doppler echocardiography was performed to measure early and late diastolic transmitral flow velocities. Tissue Doppler echocardiography was performed to measure E'. PCWP was measured with right heart catheterization. All patients were in sinus rhythm. Mean E and E' were 91+/-15 cm/s and 11+/-4 cm/s, respectively. Mean PCWP was 25+/-6 mm Hg. E' was positively correlated with PCWP (r=0.69, P=0.027). There was a significant inverse correlation between E/E' and PCWP (r=-0.74, P=0.014). Despite high left ventricular filling pressures, E/E' (mean, 9+/-4) was <15 in all but 1 patient. CONCLUSIONS: Paradoxical to the positive correlation between E/E' and PCWP in patients with myocardial disease, an inverse relationship was found in patients with CP.

Constrictive pericarditis in the modern era: evolving clinical spectrum and impact on outcome after pericardiectomy.

BACKGROUND: The clinical spectrum of constrictive pericarditis (CP) has been affected by a change in incidence of etiological factors. We sought to determine the impact of these changes on the outcome of pericardiectomy. METHODS AND RESULTS: The contemporary spectrum of CP in 135 patients (76% male) evaluated at the Mayo Clinic from 1985 to 1995 was compared with that of a historic cohort. Notable trends were an increasing frequency of CP due to cardiac surgery and mediastinal radiation and presentation in older patients (median age, 61 versus 45 years). Perioperative mortality decreased (6% versus 14%, P = 0.011), but late survival was inferior to that of an age- and sex-matched US population (57+/-8% at 10 years). The long-term outcome was predicted independently by 3 variables in stepwise logistic regression analyses: (1) age, (2) NYHA class, and most powerfully, (3) a postradiation cause. Of 90 late survivors in whom functional class could be determined, functional status had improved markedly (2.6+/-0.7 at baseline versus 1.5+/-0.8 at latest follow-up [P<0.0001]), with 83% being free of clinical symptoms. CONCLUSIONS: The evolving profile of CP, with increasingly older patients and those with radiation-induced disease in the past decade, significantly affects postoperative prognosis. Long-term results of pericardiectomy are disappointing for some patient groups, especially those with radiation-induced CP. By contrast, surgery alleviates or improves symptoms in the majority of late survivors.

Left ventricular systolic and diastolic function after pericardiectomy in patients with constrictive pericarditis: Doppler echocardiographic findings and correlation with clinical status.

OBJECTIVES: The study assessed changes in left ventricular systolic and diastolic function after pericardiectomy in patients with constrictive pericarditis and correlated postoperative Doppler echocardiographic findings with clinical status. BACKGROUND: Despite the efficacy of pericardiectomy, some patients with constrictive pericarditis fail to improve postoperatively. Data on serial evaluation of systolic and diastolic function after pericardiectomy and its relation to clinical status are not available. METHODS: From 1985 to 1995, a total of 58 patients with constrictive pericarditis underwent pericardiectomy and had at least one follow-up Doppler echocardiographic study with a respirometer: 23 patients had one examination within 3 months postoperatively, 19 had a study within 3 months and another one more than 3 months postoperatively, and 16 had one study more than 3 months postoperatively. RESULTS: In the early postoperative period, diastolic function was normal in 17 patients (40.5%), restrictive in 17 (40.5%), and constrictive in 8 (19%). Among 19 patients who had serial Doppler echocardiography, in 2 patients with restrictive physiology and 5 with constrictive physiology the results had become normal, and 1 patient who had had constrictive physiology had restrictive findings. In late follow-up, left ventricular end-diastolic diameter increased compared with preoperative measurement (p = 0.0009). Diastolic filling pattern at late follow-up was normal in 20 patients (57%), restrictive in 12 (34%) and constrictive in 3 (9%). There was a significant relationship between diastolic filling patterns and symptomatic status (chi2 = 20.9, p < 0.0001). Patients with persistent abnormal diastolic filling on Doppler echocardiography had had symptoms for a longer time preoperatively than did patients with normal diastolic physiology (p = 0.0471). CONCLUSIONS: Diastolic filling characteristics remain abnormal in a substantial number of patients with constrictive pericarditis after pericardiectomy. These abnormalities may resolve gradually but can persist. Diastolic filling abnormalities after pericardiectomy correlate well with clinical symptoms and tend to occur in patients who have had symptoms longer preoperatively. This finding supports the recommendation that pericardiectomy be performed promptly in symptomatic patients with constrictive pericarditis.

Pericardial thickness measured with transesophageal echocardiography: feasibility and potential clinical usefulness.

OBJECTIVES: This study assessed the reliability of transesophageal echocardiographic measurements of pericardial thickness and the potential diagnostic usefulness of this technique. BACKGROUND: Transthoracic echocardiography cannot reliably detect thickened pericardium. The superior resolution achieved with transesophageal echocardiography should allow better pericardial definition. METHODS: Pericardial thickness measured at 26 locations in 11 patients with constrictive pericarditis who underwent intraoperative transesophageal echocardiography was compared with pericardial thickness measured with electron beam computed tomography. Intraobserver and interobserver variabilities were determined. Pericardial thickness was then measured in 21 normal subjects. With these values as a guide, two observers reviewed 37 transesophageal echocardiographic studies to determine whether echocardiographic measurement of pericardial thickness could be used to distinguish diseased from normal pericardium. RESULTS: The correlation between echocardiographic and computed tomographic measurements (r > or = 0.95, SE < or = 0.06 mm, p < 0.0001) was excellent. The +/-2 SD limits of agreement were +/-1.0 mm or less for pericardial thickness < 5.5 mm and +/-2.0 mm or less for the entire range of thicknesses. Intraobserver and interobserver agreements were good. Mean normal pericardial thickness was 1.2 +/- 0.8 mm (+/-2 SD) and did not exceed 2.5 mm. Pericardial thickness > or = 3 mm on transesophageal echocardiography was 95% sensitive and 86% specific for the detection of thickened pericardium. CONCLUSIONS: Measurement of pericardial thickness with transesophageal echocardiography is reproducible and should be a valuable adjunct in assessing constrictive pericarditis.

Atropine augmentation in dobutamine stress echocardiography: role and incremental value in a clinical practice setting.

OBJECTIVES: This study sought to evaluate the role and incremental value of atropine in a large patient group undergoing dobutamine stress echocardiography. BACKGROUND: The use of atropine to potentiate dobutamine stress is not standard practice. Although the utility of atropine has been described, data on its incremental value remain limited and do not exist for a routine clinical practice setting. METHODS: Dobutamine stress echocardiography was performed in 1,171 patients with use of a standard protocol. Atropine (maximal dose 2.0 mg) was given to 299 patients (26%) who did not attain target heart rate. Coronary angiography was performed in 183 patients (46 received atropine), 148 of whom were found to have significant coronary artery disease (> or = 70% diameter stenosis in a major epicardial vessel, > or = 50% stenosis for left main coronary artery disease). All tests were reviewed independently by experienced observers. RESULTS: There were no major adverse events. Patients receiving atropine had a lower rest heart rate (65 vs. 74 beats/min, p < 0.0001) and more often received beta-adrenergic blocking agents (49% vs. 14%, p < 0.0001). Of 444 patients in whom stress-induced ischemia developed, 70 (16%) required atropine before ischemia became evident. Sensitivity for detection of significant coronary artery disease was 90% with dobutamine alone and 95% after the addition of atropine. In 66 patients with normal wall motion at rest, test sensitivity was 65% before and 84% after atropine was given. Atropine use did not compromise test specificity. New diagnostic information was obtained in 20 (50%) of 40 patients with angiographic coronary artery disease given atropine. Proportionately more patients with single-vessel disease required atropine before an ischemic response was observed; this effect appeared related to the higher ischemic threshold in these patients. CONCLUSIONS: Augmentation of heart rate had a modest influence on the overall diagnostic sensitivity of dobutamine stress echocardiography in our study cohort. However, it was particularly helpful in patients receiving beta-blockers and those with milder coronary disease. Despite the use of > or = 1 mg of atropine in some patients, this incremental value was not achieved at the expense of safety.

Sudden death in mitral regurgitation due to flail leaflet.

OBJECTIVES: We sought to assess the incidence and determinants of sudden death (SUD) in mitral regurgitation due to flail leaflet (MR-FL). BACKGROUND: Sudden death is a catastrophic complication of MR-FL. Its incidence and predictability are undefined. METHODS: The occurrence of SUD was analyzed in 348 patients (age 67 +/- 12 years) with MR-FL diagnosed echocardiographically from 1980 through 1994. RESULTS: During a mean follow-up of 48 +/- 41 months, 99 deaths occurred under medical treatment. Sudden death occurred in 25 patients, three of whom were resuscitated. The sudden death rates at five and 10 years were 8.6 +/- 2% and 18.8 +/- 4%, respectively, and the linearized rate was 1.8% per year. By multivariate analysis, the independent baseline predictors of SUD were New York Heart Association (NYHA) functional class (p = 0.006), ejection fraction (p = 0.0001) and atrial fibrillation (p = 0.059). The yearly linearized rate of sudden death was 1% in patients in functional class I, 3.1% in class II and 7.8% in classes III and IV. However, of 25 patients who had SUD, at baseline, 10 (40%) were in functional class I, 9 (36%) were in class II and only 6 (24%) in class III or IV. In five patients (20%), no evidence of risk factors developed until SUD. In patients with an ejection fraction > or =60% and sinus rhythm, the linearized rate of SUD was not different in functional classes I and II (0.8% per year). Surgical correction of MR (n = 186) was independently associated with a reduced incidence of SUD (adjusted hazard ratio [95% confidence interval] 0.29 [0.11 to 0.72], p = 0.007). CONCLUSIONS: Sudden death is relatively common in patients with MR-FL who are conservatively managed. Patients with severe symptoms, atrial fibrillation and reduced systolic function are at higher risk, but notable rates of SUD have been observed without these risk factors. Correction of MR appears to be associated with a reduced incidence of SUD, warranting early consideration of surgical repair.

Constrictive pericarditis and pleuropulmonary disease linked to ergot dopamine agonist therapy (cabergoline) for Parkinson's disease.

Cabergoline is one of several ergoline dopamine agonist medications used in the treatment of Parkinson's disease (PD). We diagnosed constrictive pericarditis (CP) in a patient with PD receiving cabergoline therapy (10 mg daily), who had symptoms and signs of congestive heart failure (CHF). In the absence of previous reported cases of this condition linked to ergoline drugs, cabergoline was not initially identified as the cause. Shortly thereafter, however, the patient developed of a severe pleuropulmonary inflammatory-fibrotic syndrome, a recognized complication of ergoline medications, thus suggesting a common pathogenesis due to cabergoline therapy. To our knowledge, this is the first case in the English literature, although we speculate that CP may be more common than reported among patients with PD who are treated with an ergoline drug (cabergoline, bromocriptine, pergolide, or lisuride). The diagnosis of CP is difficult and requires a high level of suspicion; symptoms may masquerade as CHF due to common mechanisms such as coronary artery disease. In patients with PD who are taking not only cabergoline but also one of the other ergoline drugs, CP should be suspected if symptoms of CHF develop.

Spontaneous aortic laceration causing flail aortic valve and acute aortic regurgitation.

Spontaneous laceration of the aorta is an unusual cause of flail aortic valve. We report a case of acute aortic regurgitation caused by flail aortic valve as a result of spontaneous laceration of the ascending aorta. The role of transesophageal echocardiography in the diagnosis of this condition is discussed.

Analysis of systolic and diastolic time intervals during dobutamine-atropine stress echocardiography: diagnostic potential of the Doppler myocardial performance index.

Systolic and especially diastolic Doppler time intervals may be early markers of myocardial ischemia inducible by dobutamine-atropine stress echocardiography (DASE). We postulated that the Doppler myocardial performance index (MPI) may help differentiate ischemic from nonischemic responses. Hemodynamic and Doppler echocardiography variables were measured prospectively at every stress level of DASE in 32 patients (mean age 67 +/- 13 years). Adequate recordings were obtained in 27 patients; 13 had an ischemic response (group I) and 14 a nonischemic response (group II). Heart rate differed between groups at baseline. At equivalent peak stress, left ventricular wall motion score index was significantly greater and ejection fraction lower in group I patients. Of the Doppler variables, only the MPI consistently differed between groups, irrespective of the number of stress levels compared. The Doppler MPI may be a useful adjunct to wall motion analysis in the detection of myocardial ischemia during DASE.

Molecular descriptors that influence the amount of drugs transfer into human breast milk.

Most drugs are excreted into breast milk to some extent and are bioavailable to the infant. The ability to predict the approximate amount of drug that might be present in milk from the drug structure would be very useful in the clinical setting. The aim of this research was to simplify and upgrade the previously developed model for prediction of the milk to plasma (M/P) concentration ratio, given only the molecular structure of the drug. The set of 123 drug compounds, with experimentally derived M/P values taken from the literature, was used to develop, test and validate a predictive model. Each compound was encoded with 71 calculated molecular structure descriptors, including constitutional descriptors, topological descriptors, molecular connectivity, geometrical descriptors, quantum chemical descriptors, physicochemical descriptors and liquid properties. Genetic algorithm was used to select a subset of the descriptors that best describe the drug transfer into breast milk and artificial neural network (ANN) to correlate selected descriptors with the M/P ratio and develop a QSAR. The averaged literature M/P values were used as the ANN's output and calculated molecular descriptors as the inputs. A nine-descriptor nonlinear computational neural network model has been developed for the estimation of M/P ratio values for a data set of 123 drugs. The model included the percent of oxygen, parachor, density, highest occupied molecular orbital energy (HOMO), topological indices (chiV2, chi2 and chi1) and shape indices (kappa3, kappa2), as the inputs had four hidden neurons and one output neuron. The QSPR that was developed indicates that molecular size (parachor, density) shape (topological shape indices, molecular connectivity indices) and electronic properties (HOMO) are the most important for drug transfer into breast milk. Unlike previously reported models, the QSPR model described here does not require experimentally derived parameters and could potentially provide a useful prediction of M/P ratio of new drugs only from a sketch of their structure and this approach might also be useful for drug information service. Regardless of the model or method used to estimate drug transfer into breast milk, these predictions should only be used to assist in the evaluation of risk, in conjunction with assessment of the infant's response.

Total occlusion of left main coronary artery in Orientals: profile of 4 cases.

The authors report 4 Oriental cases of total occlusion of the left main coronary artery (LMCA) with differing presentations. The first patient had a twelve-year history of stable angina pectoris. The second patient had angina for a year, which became unstable two months prior to diagnosis. The third patient had myocardial infarction seven years ago and presented with a one-month history of rest angina. The fourth patient had stable effort angina for six years but presented with accelerated angina three months prior to diagnosis. The incidence of total occlusion of the LMCA is rare and survival depends on the existence of collateral circulation. In LMCA disease, there is usually disease in other parts of the coronary arterial tree, and hence, the need for urgent coronary bypass surgery.

Myocardial infarction in patients aged 40 years and below: an angiographic review.

Over a period of 27 months, 32 patients aged 40 and below were admitted for acute myocardial infarction. Twenty-nine had coronary angiography with a mean of 15.7 +/- 10.0 days following infarction. Fourteen patients had single vessel, 10 multi-vessel and 5 had only minor coronary disease. Disease in the left anterior descending (LAD) artery was more common than in the circumflex or right coronary artery (RCA), but myocardial infarction occurred with near equal frequency in both the LAD and RCA territories. Only 2 infarct-related vessels were collateralized. Spontaneous coronary dissection was detected in 2 patients. The left ventricular function was significantly impaired in about half of the patients.

A review of patients with a 'normal' coronary angiogram over a 3-year period.

Over a period of 36 months, we detected 54 patients with normal coronary arteries or non-critical coronary artery stenosis within our study series of coronary angiography. We studied these patients to determine their clinical, electrocardiographic, stress testing and angiocardiographic characteristics. We detected among them a preponderance of female sex and a higher incidence of ethnic Indians. The majority of the patients studied had one or more coronary risk factors. 52% had a normal resting ECG. In those with a positive stress test and reports available for review, there is a near equal distribution of horizontal and J-type ST depression. Those patients with a positive treadmill tend to have a higher left ventricular end diastolic pressure (LVEDP) at cardiac catheterization. We also noted in this group of patients a higher proportion with a small distal left anterior descending artery. These patients also tend to have higher LVEDP even in the presence of normal left ventriculogram. Our current series suggests the possibility of raised left ventricular end-diastolic pressure and the presence of a "small distal left anterior descending artery" syndrome in association with patients with a 'false positive' treadmill test.

Echocardiographic diagnosis of quadricuspid aortic valve.

Isolated quadricuspid aortic valve is a rare congenital anomaly. We present a case diagnosed on cross-sectional echocardiography. To the best of our knowledge, this is the first case report on echocardiographically diagnosed quadricuspid aortic valve in Singapore.

Diagnosis of pacemaker lead infection using transoesophageal echocardiography: a case report.

INTRODUCTION: Vegetative lead infection is an uncommon complication of permanent pacemaker implantation. The diagnosis is difficult using conventional imaging methods. CLINICAL PICTURE: An elderly Indian woman with a history of diabetes mellitus developed Staphylococcus aureus infection after implementation of a permanent pacemaker. Following a non-diagnostic transthoracic echocardiogram, transoesophageal echocardiography was performed and showed a large vegetative mass attached to the pacemaker lead within the right atrium. TREATMENT: The pacemaker was removed and intravenous vancomycin administered for six weeks. OUTCOME: She was discharged well but demised two months later from a second episode of septicaemia. CONCLUSIONS: Pacemaker lead infection remains a challenging management problem. Transoesophageal echocardiography can facilitate its diagnosis.

Videothoracoscopic ligation of patent ductus arteriosus--a case report.

Video-assisted thoracoscopic surgical interruption (VTSI) of patent ductus arteriosus (PDA) is a relatively new technique when compared to surgical closure and transcatheter endovascular closure. Besides its minimally invasive nature, VTSI is the best option for neonates. Surgical approach may lead to late scoliosis in neonates and the vessels of neonates are too small for the transcatheter approach. VTSI potentially may prove to have lower morbidity and mortality than classic surgical closure of PDA. This article reviews the successful videothoracoscopic ligation of PDA in a 13-year-old girl.