Kalpana Prakasa

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.

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 ≥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” ≥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.

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.

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.

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.

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.

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.