Clinical features of arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in plakophilin-2.

BACKGROUND: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited cardiomyopathy characterized by right ventricular dysfunction and ventricular arrhythmias. A recent study reported mutations in PKP2, encoding the desmosomal protein plakophilin-2, associated with ARVD/C. The purpose of our study was to validate the frequency of PKP2 mutations in another large series of ARVD/C patients and to examine the phenotypic characteristics associated with PKP2 mutations. METHODS AND RESULTS: DNA from 58 ARVD/C patients was sequenced to determine the presence of mutations in PKP2. Clinical features of ARVD/C were compared between 2 groups of patients: those with a PKP2 mutation and those with no detectable PKP2 mutation. Thirteen different PKP2 mutations were identified in 25 (43%) of the patients. Six of these mutations have not been reported previously; 4 occurred in multiple, apparently unrelated, families. The mean age at presentation was lower among those with a PKP2 mutation (28+/-11 years) than in those without (36+/-16 years) (P<0.05). The age at median cumulative symptom-free survival (32 versus 42 years) and at the median cumulative arrhythmia-free survival (34 versus 46 years) was lower among patients with a PKP2 mutation than among those without a PKP2 mutation (P<0.05). Inducibility of ventricular arrhythmias on an electrophysiology study, diffuse nature of right ventricular disease, and presence of prior spontaneous ventricular tachycardia were identified as predictors of implanted cardioverter/defibrillator (ICD) intervention only among patients without a PKP2 mutation (P<0.05). CONCLUSIONS: Our study highlights the clinical relevance of PKP2 mutations in ARVD/C. Presence of a PKP2 mutation in ARVD/C correlates with earlier onset of symptoms and arrhythmia. Patients with a PKP2 mutation experience ICD interventions irrespective of the classic risk factors determining ICD intervention in ARVD/C patients.

Evolving role of multidetector computed tomography in evaluation of arrhythmogenic right ventricular dysplasia/cardiomyopathy.

The purpose of this study was to report 1 center's experience with multidetector computed tomography (MDCT) in the evaluation of patients suspected to have arrhythmogenic right ventricular (RV) dysplasia/cardiomyopathy (ARVD/C). RV dilatation/dysfunction is 1 of the most important criteria for establishing the diagnosis of ARVD/C. Cardiac magnetic resonance imaging (MRI) is the most preferred imaging modality for the diagnosis of ARVD/C. However, many patients with suspected ARVD/C have implantable cardioverter-defibrillators, prohibiting the use of MRI. Thirty-one patients (19 men; mean age 41 +/- 12 years) referred for evaluation of known or suspected ARVD/C had a complete reevaluation including contrast-enhanced cardiac MDCT at the center. Two patients underwent both cardiac MRI and MDCT. Seventeen of 31 patients met Task Force criteria for ARVD/C and were confirmed to have ARVD/C. Multidetector computed tomographic images were analyzed for qualitative and quantitative characteristic findings of ARVD/C. Increased RV trabeculation (p <0.001), RV intramyocardial fat (p <0.001), and scalloping (p <0.001) were significantly associated with the final diagnosis of ARVD/C. RV volumes, RV inlet dimensions, and RV outflow tract surface area were increased in patients with ARVD/C compared with patients who did not meet the criteria. RV and left ventricular functional analysis was performed in 2 patients. In conclusion, cardiac MDCT has a strong potential to detect many qualitative and quantitative abnormalities of the right ventricle in patients with ARVD/C. Limitations include implantable cardioverter-defibrillators and motion artifacts, along with well-known radiation and contrast-induced reaction.

Utility of tissue Doppler and strain echocardiography in arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Arrhythmogenic right ventricular dysplasia (ARVD) is a heritable cardiomyopathy characterized by the fibrofatty replacement of right ventricular (RV) myocardium leading to RV failure and arrhythmias. This study evaluated the potential utility of tissue Doppler echocardiography (TDE) and strain echocardiography (SE) to quantitatively assess RV function and their potential role in diagnosing ARVD. Images of 30 patients with ARVD (diagnosed by task force criteria) and 36 healthy controls were obtained. Peak systolic velocity, early diastolic velocity, displacement, strain rate, strain, outflow tract diameter, and fractional RV area change were measured in all subjects. Peak RV systolic velocity (6.4 +/- 2.2 vs 9 +/- 1.6 cm/s, p <0.0001), early diastolic velocity (-6.7 +/- 2.7 vs -9.4 +/- 2 cm/s, p <0.0001), displacement (13.7 +/- 5.8 vs 18.7 +/- 3.5 mm, p <0.0003), strain rate (-1 +/- 0.7 vs -2 +/- 1 s(-1), p = 0.002), and strain (-10 +/- 6% vs -28 +/- 11%, p = 0.001) were significantly lower in patients with ARVD compared with controls, respectively. Sensitivity and specificity, respectively, were 67% and 89% for systolic velocity, 77% and 71% for displacement, 73% and 87% for strain, 50% and 96% for strain rate, 53% and 93% for outflow tract diameter, and 47% and 83% for fractional area change. RV systolic velocity and displacement were significantly lower than in controls, even in the subset of patients with ARVD with apparently normal right ventricles by conventional echocardiography. Inter- and intraobserver agreement was high. In conclusion, TDE and SE enable the detection of ARVD via the quantification of RV function and may have potential clinical value in the assessment of patients with suspected ARVD. Peak RV systolic velocity <7.5 cm/s and peak RV strain <18% best identify patients with ARVD.

Marked lipomatous infiltration of the right ventricle: MRI findings in relation to arrhythmogenic right ventricular dysplasia.

OBJECTIVE: The purpose of this study was to describe the structure and function of the heart in the presence of marked lipomatous infiltration of the right ventricular wall in 13 patients referred for second opinions about fatty infiltration of the right ventricular wall and suspected arrhythmogenic right ventricular dysplasia. CONCLUSION: Lipomatous infiltration with right ventricular thickness > or = 6 mm on MRI but without regional or global functional abnormalities of the right ventricle appears to be distinct from fatty right ventricle associated with arrhythmogenic right ventricular dysplasia. The finding of right ventricular fat must be interpreted cautiously to avoid the pharmacologic and defibrillator intervention associated with management of arrhythmogenic right ventricular dysplasia.

Arrhythmogenic right ventricular dysplasia: a United States experience.

BACKGROUND: Arrhythmogenic right ventricular dysplasia (ARVD) is an inherited cardiomyopathy characterized by right ventricular dysfunction and ventricular arrhythmias. The purpose of our study was to describe the presentation, clinical features, survival, and natural history of ARVD in a large cohort of patients from the United States. METHODS AND RESULTS: The patient population included 100 ARVD patients (51 male; median age at presentation, 26 [interquartile range {IQR}, 18 to 38; range, 2 to 70] years). A familial pattern was observed in 32 patients. The most common presenting symptoms were palpitations, syncope, and sudden cardiac death (SCD) in 27%, 26%, and 23% of patients, respectively. Among those who were diagnosed while living (n=69), the median time between first presentation and diagnosis was 1 (range, 0 to 37) year. During a median follow-up of 6 (IQR, 2 to 13; range, 0 to 37) years, implantable cardioverter/defibrillators (ICD) were implanted in 47 patients, 29 of whom received an appropriate ICD discharge, including 3 patients who received the ICD for primary prevention. At follow-up, 66 patients were alive, of whom 44 had an ICD in place, 5 developed signs of heart failure, 2 had a heart transplant, and 18 were on drug therapy. Thirty-four patients died either at presentation (n=23: 21 SCD, 2 noncardiac deaths) or during follow-up (n=11: 10 SCD, 1 of biventricular heart failure), of whom only 3 were diagnosed while living and 1 had an ICD implanted. On Kaplan-Meier analysis, the median survival in the entire population was 60 years. CONCLUSIONS: ARVD patients present between the second and fifth decades of life either with symptoms of palpitations and syncope associated with ventricular tachycardia or with SCD. Diagnosis is often delayed. Once diagnosed and treated with an ICD, mortality is low. There is a wide variation in presentation and course of ARVD patients, which can likely be explained by the genetic heterogeneity of the disease.

Feasibility and variability of three dimensional echocardiography in arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Arrhythmogenic right ventricular dysplasia (ARVD/C) is a genetic cardiomyopathy characterized by fibrous fatty replacement of the right ventricular (RV) myocardium, leading to progressive RV failure and ventricular arrhythmias in young athletes. This study evaluated whether transthoracic, real-time, 3-dimensional echocardiography (3DE) can adequately assess RV morphology and function in ARVD/C by comparing 3DE with cardiac magnetic resonance (CMR), the current reference standard. Three-dimensional echocardiography was prospectively performed in 58 patients (23 with ARVD/C, 20 first-degree relatives with no ARVD/C, 8 with idiopathic ventricular tachycardia with no ARVD/C, and 7 healthy volunteers). All patients, except 15 patients with ARVD/C with implanted defibrillators, also underwent CMR. Three-dimensional echocardiography and CMR-derived RV volumes and ejection fractions were obtained by offline data analysis by blinded, independent observers. The mean age of the study group was 37 +/- 11 years (30 men). The feasibility of 3DE was high, and analyzable images were obtained in all subjects. Three-dimensional echocardiography revealed a wide variety of RV morphologic abnormalities in ARVD/C. There was a good correlation between 3DE and CMR for RV end-systolic volume (r = 0.72, p = 0.0001), RV end-diastolic volume (r = 0.50, p = 0.0001), and the RV ejection fraction (r = 0.88, p = 0.001). We found high intraobserver and moderate interobserver correlations for 3DE estimations of volumes and ejection fractions. In conclusion, 3DE measurements of RV volumes and ejection fractions closely correlate with CMR values and may be useful in the follow-up of patients with ARVD/C.

Electrocardiographic features of arrhythmogenic right ventricular dysplasia/cardiomyopathy according to disease severity: a need to broaden diagnostic criteria.

BACKGROUND: The purpose of this study was to systematically study diagnostic and prognostic electrocardiographic (ECG) characteristics of arrhythmogenic right ventricle dysplasia/cardiomyopathy (ARVD/C). METHODS AND RESULTS: The patient population included 50 patients with ARVD/C (27 males, 23 females; mean age 38+/-15 years). We also analyzed the ECG of 50 age- and gender-matched normal control subject and 28 consecutive patients who presented with right ventricular outflow tract (RVOT) tachycardia. Right bundle-branch block (RBBB) was present in 11 patients (22%). T-wave inversions in V1 through V3 were observed in 85% of ARVD/C patients in the absence of RBBB compared with none in RVOT and normal controls, respectively (P<0.0001); epsilon waves were seen in 33%, and a QRS duration > or =110 ms in V1 through V3 was present in 64% of patients. Among those without RBBB, our newly proposed criterion of "prolonged S-wave upstroke in V1 through V3" > or =55 ms was the most prevalent ECG feature (95%) and correlated with disease severity and induction of VT on electrophysiological study. This feature also best distinguished ARVD/C (diffuse and localized) from RVOT. CONCLUSIONS: A prolonged S-wave upstroke in V1 through V3 is the most frequent ECG finding in ARVD/C and should be considered as a diagnostic ECG marker.

Regional differences in systolic and diastolic function in arrhythmogenic right ventricular dysplasia/cardiomyopathy using magnetic resonance imaging.

Global and regional biventricular functions were analyzed in 14 patients diagnosed with arrhythmogenic right ventricular dysplasia/cardiomyopathy using cine magnetic resonance imaging and compared with similar data from 18 age-matched controls. In this study, we report results of quantitative evaluation of biventricular global and regional function using peak ejection rate and peak filling rate as measures of systolic and diastolic function, respectively (volumetric method).

Predictors of appropriate implantable defibrillator therapies in patients with arrhythmogenic right ventricular dysplasia.

BACKGROUND: Arrhythmogenic right ventricular dysplasia (ARVD) is an inherited cardiomyopathy characterized by ventricular arrhythmias and sudden cardiac death. The risk factors for sudden death and indications for implantable cardioverter-defibrillator (ICD) placement in patients with ARVD are not well defined. OBJECTIVES: The purpose of this study was to determine which clinical and electrophysiologic variables best predict appropriate ICD therapies in patients with ARVD. Particular attention focused on whether the ICD was implanted for primary or second prevention. METHODS: We enrolled 67 patients (mean age 36 +/- 14 years) with definite or probable ARVD who had undergone ICD placement. Appropriate ICD therapies were recorded, and Kaplan-Meier analysis was used to compare the event-free survival time between patients based upon the indication for ICD placement (primary vs secondary prevention), results of electrophysiologic testing, and whether the patient had probable or definite ARVD. RESULTS: Over a mean follow-up of 4.4 +/- 2.9 years, 40 (73%) of 55 patients who met task force criteria for ARVD and 4 (33%) of 12 patients with probable ARVD had appropriate ICD therapies for ventricular tachycardia/ventricular fibrillation (VT/VF; P = .027). Mean time to ICD therapy was 1.1 +/- 1.4 years. Eleven of 28 patients who received an ICD for primary prevention (39%) and 33 of 35 patients who received an ICD for secondary prevention (85%) experienced appropriate ICD therapies (P = .001). Electrophysiologic testing did not predict appropriate ICD interventions in patients who received an ICD for primary prevention. Fourteen patients (21%) received ICD therapy for life-threatening (VT/VF >240 bpm) arrhythmias. There was no difference in the incidence of life-threatening arrhythmias in the primary and secondary prevention groups (P = .29). CONCLUSION: Patients who meet task force criteria for ARVD are at high risk for sudden cardiac death and should undergo ICD placement for primary and secondary prevention, regardless of electrophysiologic testing results. Further research is needed to confirm that a low-risk subset of patients who may not require ICD placement can be identified.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a genetic cardiomyopathy characterized by ventricular arrhythmias and structural abnormalities of the right ventricle (RV). The most important aspect in the treatment of ARVD/C is establishing a correct diagnosis based on the International Task Force criteria. In our experience, cardiologists are not aware of these diagnostic criteria for ARVD/C and place too much importance on the results of magnetic resonance imaging of the RV. Patients with ARVD/C generally all have an abnormal 12-lead electrocardiogram, abnormal echocardiogram, and ventricular arrhythmias with a left bundle branch block morphology. If noninvasive testing suggests ARVD, invasive testing with an RV angiogram, RV biopsy, and electrophysiology study are recommended. We encourage patients to participate in the National Institutes of Health-sponsored multicenter clinical trial of ARVD/C (http://www.ARVD.comorhttp://www.ARVD.org). Once a diagnosis of ARVD/C is established, the main treatment decision involves whether to implant an implantable cardioverter-defibrillator (ICD). ICDs are recommended for patients who have experienced syncope, sudden death, or a sustained ventricular arrhythmia, and also for patients with overt evidence of ARVD, particularly if the electrophysiology study is abnormal or there is a family history of sudden death. We also recommend treatment of patients with ARVD/C with beta blockers and angiotensin-converting enzyme inhibitors, and that all patients with ARVD/C be screened for a mutation in the gene for plakophilin-2, because this is present in more than one third of patients with ARVD/C and may be helpful in the management of first-degree relatives.

Electrocardiographic changes in obstructive sleep apnea syndrome.

The acute electrocardiographic changes during apneic episodes in patients with sleep apnea are well known. Long-term electro-cardiographic changes in these patients are not well studied. We conducted a retrospective case-control study to assess the electrocardiographic changes in African-American patients with established obstructive sleep apnea syndrome (OSA). A significant percentage of patients with OSA had abnormal EKGs as compared to the control group. The effect of sleep apnea on the cardiovascular system is more complex in African-Americans due to higher prevalence of co-morbid conditions. Seventy-three percent of our patients with OSA had metabolic syndrome.

Cardiotoxicities of paclitaxel in African Americans.

PURPOSE: To assess the cardiac disturbances in African-American patients treated with paclitaxel. PATIENTS AND METHODS: One-hundred-nineteen African-American patients received paclitaxel for various cancers at Howard University Hospital during the years 1993-2001. Medical records of 100 patients were available for review. Sixty-seven percent were women and 33% were men. Ages ranged between 26-85 years (mean age 51 years). Medical records were reviewed for demographics, types of cancer, dosage and frequency of paclitaxel and other chemotherapeutic agents, events during paclitaxel infusion, initial and subsequent EKGs, and hospital admissions. We used the Chi-square test to compare EKG changes in patients with and without cardiac risk factors. RESULTS: Ninety patients received paclitaxel as second-line chemotherapy, and 10 patients were treated with paclitaxel as a single agent. Dosage of paclitaxel ranged from 75-200 mg/square meter and was administered every 1-3 weeks. The electrocardiogram readings revealed the following cardiac events: 26% sinus tachycardia, 13% non-specific T-wave changes, 6% myocardial infarction, 4% prolonged QT interval, 4% left-bundle branch block, 3% right-bundle branch block, 3% sinus bradycardia, 2% premature atrial contractions, 2% premature ventricular contractions, 2% atrial flutter, and 1% atrial fibrillation. Eighty percent of the patients had risk factors for coronary artery disease. These cardiac disturbances were observed from day one to a maximum of eight years after receiving the chemotherapy and were independent of dosage of paclitaxel. Sixty percent of our study population had underlying co-morbid conditions, such as dehydration, anemia, sepsis, and hypoxia. The EKG changes observed in patients with underlying cardiac risk factors were statistically significant (p<0.0001). CONCLUSION: Paclitaxel was not associated with significant symptomatic cardiac disturbances during infusion in our study population. Caution should be exercised in patients with underlying cardiac disease and risk factors for coronary artery disease. However more prospective studies with closer follow-up during paclitaxel infusion are needed to assess its cardiotoxicities.

A systematic review of venous thromboembolism prophylaxis strategies in patients with renal insufficiency, obesity, or on antiplatelet agents.

BACKGROUND: There is uncertainty about optimal strategies for venous thromboembolism (VTE) prophylaxis among select populations such as patients with renal insufficiency, obesity, or patients taking antiplatelet drugs including aspirin. Their physiologies make prophylaxis particularly challenging. PURPOSE: We performed a comparative effectiveness review of the literature on efficacy and safety of VTE prophylaxis in these populations. DATA SOURCES: We searched MEDLINE, EMBASE, SCOPUS, CINAHL, International Pharmaceutical Abstracts, clinicaltrial.gov, and the Cochrane Library through August 2012. Eligible studies included controlled trials and observational studies. DATA EXTRACTION: Two reviewers evaluated studies for eligibility, serially abstracted data, and independently evaluated the risk of bias and strength of evidence supporting interventions to prevent VTE in these populations. RESULTS: After a review of 30,902 citations, we identified 9 controlled studies, 5 of which were trials, and the other 4 were observational studies. Five articles addressed prophylaxis of patients with renal insufficiency, 2 addressed obese patients, and 2 addressed patients on antiplatelet agents. No study tested prophylaxis in underweight patients or those with liver disease. The majority of observational studies had a high risk of bias. The strength of evidence ranged from low to insufficient regarding the comparative effectiveness and safety of VTE prophylaxis among these patients. CONCLUSION: The current evidence is insufficient regarding optimal VTE prophylaxis for patients with renal insufficiency, obesity, or those who are on antiplatelet drugs including aspirin. High-quality studies are needed to inform clinicians about the best VTE prophylaxis for these patients.

Pharmacologic and mechanical strategies for preventing venous thromboembolism after bariatric surgery: a systematic review and meta-analysis.

We sought to assess the comparative effectiveness and safety of pharmacologic and mechanical strategies to prevent venous thromboembolism (VTE) in patients undergoing bariatric surgery. We searched (through August 2012) for primary studies that had at least 2 different interventions. Of 30,902 citations, we identified 8 studies of pharmacologic strategies and 5 studies of filter placement. No studies randomized patients to receive different interventions. One study suggested that low-molecular-weight heparin is more efficacious than unfractionated heparin in preventing VTE (0.25% vs 0.68%, P < .001), with no significant difference in bleeding. One study suggested that prolonged therapy (after discharge) with enoxaparin sodium may prevent VTE better than inpatient treatment only. There was insufficient evidence supporting the hypothesis that filters reduce the risk of pulmonary embolism, with a point estimate suggesting increased rates with filters (pooled relative risk [RR], 1.21 95% CI, 0.57-2.56). There was low-grade evidence that filters are associated with higher mortality (pooled RR, 4.30 95% CI, 1.60-11.54) and higher deep vein thrombosis rates (2.94 1.35-6.38). There was insufficient evidence to support that augmented subcutaneous enoxaparin doses (>40 mg daily or 30 mg twice daily) are more efficacious than standard dosing, with a trend toward increased bleeding. Of note, for both filters and augmented pharmacologic dosing strategies, patients at highest risk for VTE were more likely to receive more intensive interventions, limiting our ability to attribute outcomes to prophylactic strategies used.

Prevalence and pathophysiologic attributes of ventricular dyssynchrony in arrhythmogenic right ventricular dysplasia/cardiomyopathy.

OBJECTIVES: This study sought to investigate the prevalence and mechanisms underlying right ventricular (RV) dyssynchrony in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) using tissue Doppler echocardiography (TDE). BACKGROUND: An ARVD/C is characterized by fibrofatty replacement of RV myocardium and RV dilation. These pathologic changes may result in electromechanical dyssynchrony. METHODS: Echocardiography, both conventional and TDE, was performed in 52 ARVD/C patients fulfilling Task Force criteria and 25 control subjects. The RV end-diastolic and -systolic areas, right ventricular fractional area change (RVFAC), and left ventricular (LV) volumes and function were assessed. Mechanical synchrony was assessed by measuring differences in time-to-peak systolic velocity (T(SV)) between the RV free wall, ventricular septum, and LV lateral wall. An RV dyssynchrony was defined as the difference in T(SV) between the RV free wall and the ventricular septum, >2 SD above the mean value for control subjects. RESULTS: The mean difference in RV T(SV) was higher in ARVD/C compared with control subjects (55 +/- 34 ms vs. 26 +/- 15 ms, p < 0.001). Significant RV dyssynchrony was not noted in any of the control subjects. Based on a cutoff value of 56 ms, significant RV dyssynchrony was present in 26 ARVD/C patients (50%). Patients with RV dyssynchrony had a larger RV end-diastolic area (22 +/- 5 cm(2) vs. 19 +/- 4 cm(2), p = 0.02), and lower RVFAC (29 +/- 8% vs. 34 +/- 8%, p = 0.03) compared with ARVD/C patients without RV dyssynchrony. No differences in QRS duration, LV volumes, or function were present between the 2 groups. CONCLUSIONS: An RV dyssynchrony may occur in up to 50% of ARVD/C patients, and is associated with RV remodeling. This finding may have therapeutic and prognostic implications in ARVD/C.

Comparison of novel echocardiographic parameters of right ventricular function with ejection fraction by cardiac magnetic resonance.

BACKGROUND: Assessment of right ventricular (RV) function by echocardiography is challenging. Newer techniques such as tissue Doppler echocardiography and strain echocardiography may allow accurate and quantitative assessment of RV function. We sought to determine which echocardiographic variable or variables best correlated with RV ejection fraction (RVEF) by cardiac magnetic resonance. METHODS: We performed conventional echocardiography, tissue Doppler echocardiography, strain echocardiography, and cardiac magnetic resonance on 53 individuals, of which 10 patients had arrhythmogenic RV dysplasia without pulmonary hypertension, and 43 were control subjects. RV fractional area change (FAC), Tei index, isovolumic acceleration, peak systolic velocity (S'), tissue displacement, systolic strain (Ss) rate, and Ss were measured. RESULTS: RVEF, FAC, S', tissue displacement, isovolumic acceleration, Ss rate, and Ss were significantly lower in patients compared with control subjects (P < or = .05 in all) but not the Tei index (P = .07). Regression analysis revealed a significant correlation between S', tissue displacement, Ss rate, Ss, and FAC with RVEF (P < .05 for all) but not with isovolumic acceleration and Tei index (P = .13 and .39, respectively). Multivariate analysis demonstrated a persistent significant relationship between S' and FAC with RVEF (both P < .05). However, feasibility, and intraobserver and interobserver agreement, were substantially lower for FAC. A cut-off value of 8.8 cm/s for S' had sensitivity and specificity of 80% and 79% (area under the curve 0.87, P = .01), respectively, for prediction of RVEF less than 45%. CONCLUSION: Tissue Doppler echocardiographically derived S' best correlates with cardiac magnetic resonance-derived RVEF with high reproducibility and may facilitate simple and quantitative assessment of RV function.

Long-term efficacy of catheter ablation of ventricular tachycardia in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy.

OBJECTIVES: This study sought to evaluate the outcomes of radiofrequency catheter ablation (RFA) of ventricular tachycardia (VT) in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) patients. Particular focus was placed on defining the single-procedure efficacy over long-term follow-up. BACKGROUND: ARVD/C is an inherited cardiomyopathy characterized by VT and right ventricular dysfunction. Prior single-center studies have reported conflicting results concerning the efficacy of RFA of VT in ARVD/C patients. METHODS: The study population comprised 24 patients (age 36 +/- 9 years, 11 male), enrolled in the Johns Hopkins ARVD registry, who underwent 1 or more RFA procedures for treatment of VT. Patients were followed up for 32 +/- 36 months (range 1 day to 12 years). Recurrence was defined as the documentation of VT subsequent to the procedure. RESULTS: A total of 48 RFA procedures were performed using 3-dimensional electroanatomical (n = 10) or conventional (n = 38) mapping. Of these procedures, 22 (46%), 15 (31%), and 11 (23%) resulted in elimination of all inducible VTs, clinical VT but not all, and none of the inducible VTs, respectively. Forty (85%) procedures were followed by recurrence. The cumulative VT recurrence-free survival was 75%, 50%, and 25% after 1.5, 5, and 14 months, respectively. The cumulative VT recurrence-free survival did not differ by procedural success, mapping technique, or repetition of procedures. There was 1 procedure-related death. CONCLUSIONS: Our study shows a high rate of recurrence in ARVD/C patients undergoing RFA of VT. This likely reflects the fact that ARVD/C is a diffuse cardiomyopathy with progressively evolving electrical substrate. Further studies are needed to define the precise role of RFA of VT in ARVD/C.

Penetrance of mutations in plakophilin-2 among families with arrhythmogenic right ventricular dysplasia/cardiomyopathy.

OBJECTIVES: The purpose of our study was to characterize the penetrance of PKP2 mutations among family members of people with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) and to examine clinical features and predictors of disease among PKP2 mutation carriers. BACKGROUND: Arrhythmogenic right ventricular dysplasia/cardiomyopathy is an inherited cardiomyopathy characterized by fatty-fibrous myocardial replacement of the right ventricle, ventricular arrhythmias, and right ventricular dysfunction. Mutations in PKP2, the gene encoding plakophilin-2, are found in 11% to 43% of ARVD/C probands. METHODS: The study population was composed of 64 individuals in 9 families with an ARVD/C proband previously shown to carry a pathogenic PKP2 mutation. The diagnosis of ARVD/C was established based on task force criteria (TFC) set by the European Society of Cardiology. RESULTS: In addition to the probands, PKP2 mutations were present in 52% of relatives screened. Forty-nine percent of PKP2 mutation carriers met TFC. Among mutation carriers who did not meet full TFC, 50% met at least some TFC criteria besides family history. Pedigrees showed wide intra-familial variability, ranging from severe disease with early death to individuals who were completely asymptomatic late in life. Male PKP2 mutation carriers were more likely to have structural and conduction abnormalities as determined by imaging studies, signal-averaged electrocardiography, and 24-h ambulatory electrocardiography (p < 0.05). CONCLUSIONS: PKP2 mutations in a group of North American families with ARVD/C have both reduced penetrance and variable expressivity. Gender may have an influence on penetrance of PKP2 mutations, with male mutation carriers more likely to develop specific phenotypic manifestations of this disease.