The clinical profile of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) patients with late presentation is unknown.
The purpose of this study was to characterize the genotype, ...cardiac phenotype, and long-term outcomes of ARVC/D patients with late presentation (age ≥50 years at diagnosis).
Five hundred two patients with an ARVC/D diagnosis from Johns Hopkins and Utrecht Registries were studied and long-term clinical outcomes ascertained.
Late presentation was seen in 104 patients (21%; 38% PKP2 carriers); 3% were ≥65 years at diagnosis. Sustained ventricular tachycardia was the major (43%) mode of presentation in patients with late presentation, whereas cardiac syncope was infrequent (P <.001). Those with late presentation were significantly less likely to harbor a known pathogenic mutation (53%; P = .005), have less precordial T-wave repolarization changes (P <.001), and have lower ventricular ectopy burden (P = .026). Over median 6-year follow-up, 68 patients with late presentation (65%) experienced sustained ventricular arrhythmias, with similar arrhythmia-free survival at 5-year follow up (P = .48). Left ventricular dysfunction and heart failure were seen in 24 (32%) and 15 patients (14%), respectively, without need for cardiac transplantation. In the late presentation cohort, male sex, pathogenic mutation, right ventricular structural disease, lack of family history, and electrophysiologic study inducibility were associated with increased arrhythmic risk.
One-fifth of all ARVC/D patients present after age 50 years, often with sustained ventricular tachycardia, and are less likely to have prior syncope, ECG changes, ventricular ectopy, or identifiable pathogenic mutation. In ARVC/D, late presentation does not confer a benign prognosis and is associated with high arrhythmic risk.
Abstract Objectives The aims of this study were to determine the clinical characteristics and outcomes of pediatric-onset arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) and to ...compare these with those of adult-onset ARVD/C. Background Improved early detection and increased awareness of ARVD/C have led to a growing group of pediatric patients seeking management recommendations. Prior studies have mainly included adults with ARVD/C; however, clinical features and outcomes may differ in pediatric subjects. Methods Among 502 subjects fulfilling task force criteria for ARVD/C, we identified 75 (15%) with pediatric-onset disease (diagnosis at <18 years of age or probands presenting symptomatically at <18 years of age). Clinical characteristics and outcomes (sustained ventricular tachycardia, cardiac transplantation, and death) were compared between pediatric and adult patients. Results Pediatric patients presented at 15.3 ± 2.4 years of age. Most pediatric patients were male (55%) and ARVD/C-associated mutation carriers (80%). One-fourth of pediatric patients presented with sudden cardiac death (15%) or resuscitated sudden cardiac arrest (11%). Compared with adults, pediatric patients were disproportionately mutation carriers (p = 0.002) but not more often male (p = 0.696) or probands (p = 0.371). Pediatric patients were more likely to present with sudden cardiac death (p = 0.003), whereas adults more often presented with sustained ventricular tachycardia (p = 0.017). There were no other phenotypic differences between the groups. During 8.4 ± 7.5 years of follow-up, survival free from sustained ventricular tachycardia (p = 0.359), cardiac transplantation (p = 0.523), and death (p = 0.359) was similar between pediatric and adult patients. Conclusions Pediatric patients with ARVD/C are typically male mutation carriers presenting in adolescence. Pediatric patients disproportionately present with sudden cardiac death. However, once diagnosed, clinical characteristics and outcomes are similar between pediatric and adult patients.
Summary Background We compared standard adjuvant anthracycline chemotherapy with anthracycline–taxane combination chemotherapy in women with operable node-positive breast cancer. Here we report the ...final, 10-year follow-up analysis of disease-free survival, overall survival, and long-term safety. Methods BCIRG 001 was an open label, phase 3, multicentre trial in which 1491 patients aged 18–70 years with node-positive, early breast cancer and a Karnofsky score of 80% or more were randomly assigned to adjuvant treatment with docetaxel, doxorubicin, and cyclophosphamide (TAC) or fluorouracil, doxorubicin, and cyclophosphamide (FAC) every 3 weeks for six cycles. Randomisation was stratified according to institution and number of involved axillary lymph nodes per patient (one to three vs four or more). Disease-free survival was the primary endpoint and was defined as the interval between randomisation and breast cancer relapse, second primary cancer, or death, whichever occurred first. Efficacy analyses were based on the intention-to-treat principle. BCIRG 001 is registered with ClinicalTrials.gov , number NCT00688740. Findings Enrolement took place between June 11, 1997 and June 3, 1999; 745 patients were assigned to receive TAC and 746 patients were assigned to receive FAC. After a median follow-up of 124 months (IQR 90–126), disease-free survival was 62% (95% CI 58–65) for patients in the TAC group and 55% (51–59) for patients in the FAC group (hazard ratio HR 0·80, 95% CI 0·68–0·93; log-rank p=0·0043). 10-year overall survival was 76% (95% CI 72–79) for patients in the TAC group and 69% (65–72) for patients in the FAC group (HR 0·74, 0·61–0·90; log-rank p=0·0020). TAC improved disease-free survival relative to FAC irrespective of nodal, hormone receptor, and HER2 status, although not all differences were significant in these subgroup analyses. Grade 3–4 heart failure occurred in 26 (3%) patients in the TAC group and 17 (2%) patients in the FAC group, and caused death in two patients in the TAC group and four patients in the FAC group. A substantial decrease in left ventricular ejection fraction (defined as a relative decrease from baseline of 20% or more) was seen in 58 (17%) patients who received TAC and 41 (15%) patients who received FAC. Six patients who received TAC developed leukaemia or myelodysplasia, as did three patients who received FAC. Interpretation Our results provide evidence that the initial therapeutic outcomes seen at the 5-year follow-up with a docetaxel-containing adjuvant regimen are maintained at 10 years. However, a substantial percentage of patients had a decrease in left ventricular ejection fraction, probably caused by anthracycline therapy, which warrants further investigation. Funding Sanofi.
Cardiovascular outcomes in type 2 diabetes. A double-blind placebo-controlled study of bezafibrate: the St. Mary's, Ealing,
Northwick Park Diabetes Cardiovascular Disease Prevention (SENDCAP) Study.
...R S Elkeles ,
J R Diamond ,
C Poulter ,
S Dhanjil ,
A N Nicolaides ,
S Mahmood ,
W Richmond ,
H Mather ,
P Sharp and
M D Feher
St. Mary's Hospital, London, U.K.
Abstract
OBJECTIVE: To determine whether serum lipid intervention, in addition to conventional diabetes treatment, could alter cardiovascular
outcomes in type 2 diabetes. RESEARCH DESIGN AND METHODS: There were 164 type 2 diabetic subjects (117 men, 47 women) without
a history of clinical cardiovascular disease randomized to receive either bezafibrate or placebo daily on a double-blind basis
in addition to routine diabetes treatment and followed prospectively for a minimum of 3 years. Serial biochemical and noninvasive
vascular assessments, carotid and femoral artery B-mode ultrasound measurements, and those pertaining to coronary heart disease
(CHD)--clinical history, the World Health Organization (WHO) cardiovascular questionnaire, and resting and exercise electrocardiogram
(ECG)--were recorded. RESULTS: Bezafibrate treatment was associated with significantly greater reductions over 3 years in
median serum triglyceride (-32 vs. 4%, P = 0.001), total cholesterol (-7 vs. -0.3%, P = 0.004), and total-to-HDL cholesterol
ratio (-12 vs. -0.0%, P = 0.001), and an increase in HDL cholesterol (6 vs. -2%, P = 0.02) as compared with placebo. There
was a trend toward a greater reduction of fibrinogen (-18 vs. -6%, P = 0.08) at 3 years. No significant differences between
the two groups were found in the progress of ultrasonically measured arterial disease. In those treated with bezafibrate,
there was a significant reduction (P = 0.01, log-rank test) in the combined incidence of Minnesota-coded probable ischemic
change on the resting ECG and of documented myocardial infarction. CONCLUSIONS: Improving dyslipidemia in type 2 diabetic
subjects had no effect on the progress of ultrasonically measured arterial disease, although the lower rate of "definite CHD
events" in the treated group suggests that this might result in a reduction in the incidence of coronary heart disease.
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