Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is frequently associated with desmosomal mutations. However, nondesmosomal mutations may be involved. The aim of this study was to ...assess the contribution of a phospholamban (PLN) gene mutation to ARVD/C diagnosis according to the revised 2010 task force criteria (TFC). In 142 Dutch patients (106 men, mean age 51 ± 13 years) with proven ARVD/C (fulfillment of 2010 TFC for diagnosis), 5 known desmosomal genes (PKP2, DSP, DSC2, DSG2, and JUP) and the nondesmosomal PLN gene were screened. After genetic analysis, phenotypic characteristics of desmosomal versus PLN mutation carriers were compared. In 59 of 142 patients with ARVD/C (42%), no desmosomal mutation was found. In 19 of 142 patients (13%), the PLN founder mutation c.40_42delAGA (p.Arg14del) was identified. PLN mutation carriers more often had low-voltage electrocardiograms (p = 0.004), inverted T waves in leads V4 to V6 (p <0.001), and additional structural (p = 0.007) or functional (p = 0.017) left ventricular impairment, whereas desmosomal mutation carriers had more solitary right ventricular abnormalities. The revised TFC included 21 of 142 patients with proven ARVD/C who did not meet the 1994 TFC, including 7 PLN mutation carriers. In conclusion, there is a substantial contribution of PLN mutation to ARVD/C diagnosis by the 2010 TFC. In 32% of patients (19 of 59) with genetically unexplained proven ARVD/C, this nondesmosomal mutation was found. PLN mutation carriers have ARVD/C characteristics, including important right ventricular involvement, and additionally more often low-voltage electrocardiograms, inverted T waves in the left precordial leads, and left ventricular involvement.
To compare the long-term efficacy and safety of sirolimus-eluting stents (SES) to those of bare-metal stents (BMS) for ST-segment elevation myocardial infarction, outcomes were assessed in 310 ...patients (mean age age 59 ± 11 years, 78% men) included in the randomized MISSION! Intervention Study: A Prospective Randomised Controlled Trial to Evaluate the Efficacy of Drug-Eluting Stents Versus Bare-Metal Stents for the Treatment of Acute Myocardial Infarction after a median follow-up period of 38 months. All patients were treated with aspirin (lifelong) and clopidogrel for 1 year after stent implantation. Except for a significant difference between reference vessel diameters (SES 2.76 mm vs BMS 2.92 mm, p = 0.02), there were no significant differences in baseline and angiographic characteristics between the treatment groups (158 SES, 152 BMS). A significant difference between SES and BMS patients for all revascularization end points was found after the first year of follow-up. However, at 3 years of follow-up, although there was still a trend toward better clinical outcomes in SES-treated patients, differences were no longer significant (death 4.4% vs 6.6%, p = 0.41; target vessel–related myocardial infarction 2.5% vs 4.6%, p = 0.32; target vessel revascularization 8.9% vs 15.8%, p = 0.06), target lesion revascularization 6.3% vs 12.5%, p = 0.06; and target vessel failure 12.0% vs 19.7%, p = 0.06). Three cases of very late (definite) stent thrombosis were observed in the SES group (1.9%) versus none in the BMS group (p = 0.14). In conclusion, the significant SES benefit (compared to BMS) in patients with ST-segment elevation myocardial infarctions at 1-year follow-up in terms of target vessel revascularizations decreased to some extent because of more similar target vessel revascularization rates during the 2 subsequent years. Rates of death and nonfatal recurrent MI remained comparable.
Background We recently demonstrated in a randomized, double-blind, placebo-controlled trial that intramyocardial bone marrow cell (BMC) injection is associated with improvements in myocardial ...perfusion and anginal symptoms in chronic myocardial ischemia patients. In the present study the results of the crossover phase of this trial, in which patients previously treated with placebo received autologous BMC injections are reported. This allows a unique intra-patient comparison on the effect of BMC versus placebo injection with elimination of patient-related confounding factors. Methods In 16 patients (14 male, 64 ± 10 years), who previously received intramyocardial placebo injections in the setting of a randomized trial, 100 × 106 BMC were injected using the NOGA-system. Canadian Cardiovascular Society angina score and quality of life were evaluated at baseline, 3 and 6 months. Tc-99m single photon emission computed tomography and magnetic resonance imaging were performed at baseline and 3 months to assess myocardial perfusion and left ventricular (LV) function. Results Canadian Cardiovascular Society score and quality of life improved significantly after BMC injection as compared to placebo ( P = 0.01 and P = 0.02, respectively). Single photon emission computed tomography revealed a significant greater improvement ( P = 0.03) in summed stress score after BMC injection as compared to placebo. LV end-systolic volume significantly decreased after BMC injection but not after placebo injection. LV end-diastolic volume and LV ejection fraction did not change. Conclusion Intramyocardial BMC injection in patients with chronic myocardial ischemia who previously received intramyocardial placebo treatment resulted in significant improvement in angina symptoms and myocardial perfusion. These results confirm the outcome of our previously reported randomized trial.
The present study investigated the safety, feasibility, and potential efficacy of autologous bone marrow cell injection in patients with chronic myocardial infarction and severe left ventricular (LV) ...dysfunction. In 15 patients (63 ± 9 years; 14 men) bone marrow was aspirated from the iliac crest. Using the NOGA system (Biosense-Webster, Waterloo, Belgium), 94 ± 14 × 106 bone marrow–derived mononuclear cells were injected into the infarction border zone. Bone marrow cell injection was performed without periprocedural complications in all patients. At 2.5 months, 1 patient died from worsening heart failure. New York Heart Association class improved from 3.5 ± 0.5 at baseline to 2.7 ± 0.8 at 3 months (p <0.01) and 2.9 ± 0.8 at 6 months (p <0.01 vs baseline). LV ejection fraction (technetium-99m tetrofosmin single-photon emission computed tomography) increased from 23 ± 8% to 27 ± 9% at 3 months (p = 0.02) and regional wall thickening improved from 12.8 ± 5.9% to 15.3 ± 7.2% at 3 months (p = 0.02). Injected myocardial segments displayed a significant improvement in regional wall thickening (6.6 ± 6.3% vs 11.7 ± 7.0% at 3 months, p <0.01) and perfusion score (3.5 ± 0.7 vs 3.0 ± 0.9 at 3 months, p = 0.02) and a trend toward an improved fluorine-18 fluorodeoxyglucose score (2.9 ± 0.9 vs 2.6 ± 1.0 at 3 months, p = 0.06). Regional wall thickening (16.5 ± 8.9% vs 19.1 ± 9.1% at 3 months, p = NS), perfusion score (1.8 ± 0.4 vs 1.7 ± 0.5 at 3 months, p = NS), and fluorodeoxyglucose score (1.7 ± 0.4 vs 1.6 ± 0.4 at 3 months, p = NS) did not improve in noninjected myocardial segments. In conclusion, bone marrow cell injection in patients with chronic myocardial infarction and severe LV dysfunction is safe and feasible and appears to be associated with a decrease in heart failure symptoms and an improved LV function.
In acute myocardial infarction cardiac troponin-T (cTnT) is the preferred biomarker to detect myocardial necrosis. Our aim was to investigate the prognostic value of peak plasma cTnT in patients with ...ST-elevation myocardial infarction treated by primary percutaneous coronary intervention (PCI). Patients were eligible if ST-elevation myocardial infarction symptoms started <9 hours before the primary PCI. During the first 48 hours after primary PCI, cTnT and creatine kinase were measured repeatedly. Main outcome measures were left ventricular ejection fraction assessed by myocardial scintigraphy at 90 days, and clinical outcomes through 1-year follow-up after primary PCI in a dedicated outpatient clinic; 168 consecutive patients (79% men) with first ST-elevation myocardial infarction were studied. Mean age ± SD was 59 ± 12 years. Peak cTnT values were reached within 24 hours after primary PCI in all patients. The enzymatic infarct size, measured by cumulative 48-hours creatine kinase release, correlated positively with peak cTnT (r = 0.73, p <0.001). Left ventricular ejection fraction at 3 months was negatively correlated with peak cTnT (r = −0.52, p <0.001). A peak plasma cTnT ≥6.5 μg/L predicted a left ventricular ejection fraction ≤40% at follow-up with 86% sensitivity and 74% specificity. Multivariable Cox regression analysis identified peak cTnT as an independent predictor of major adverse cardiac events (hazard ratio 1.07, 95% confidence limits 1.01 to 1.12) and heart failure (hazard ratio 1.12, 95% confidence limits 1.05 to 1.20) during follow-up. In conclusion, peak cTnT after primary PCI for ST-elevation myocardial infarction offers a good estimation of infarct size and is a prognostic indicator in patients with first acute myocardial infarction.
Alcohol septal ablation (ASA) aims to decrease left ventricular outflow tract (LVOT) obstruction in patients with obstructive hypertrophic cardiomyopathy (HC). To date, no diagnostic variables at ...baseline are available to predict long-term success of the procedure. We hypothesized that an immediate decrease in septal longitudinal strain after ASA would be associated with sustained LVOT gradient decrease after 6 months. ASA was performed in 22 patients with HC and severe drug-refractory symptoms. Clinical evaluation and 2-dimensional echocardiography were performed before, 1 day after, and 6 months after ASA. During 6-month follow-up, New York Heart Association class improved (2.7 ± 0.5 vs 1.4 ± 0.6, p <0.01) and LVOT gradient decreased (68 ± 31 vs 21 ± 21 mm Hg, p <0.01). Strain evaluation showed considerable decreases in basal septal strain (−12 ± 3% vs −8 ± 2%, p <0.01) and midseptal strain (−13 ± 4% vs −8 ± 3%, p <0.01) 1 day after ASA. Decreases in basal septal and midseptal strain 1 day after ASA were strongly related to the decrease in LVOT gradient during 6-month follow-up (r = 0.70, p <0.01, and r = 0.65, p <0.01, respectively). In conclusion, in patients with HC and severe drug-refractory symptoms, immediate decrease in septal strain after ASA is strongly related to a decrease in LVOT gradient after 6 months and might therefore serve as an early determinant for long-term success of the ASA procedure.
Sirolimus-Eluting Stents Versus Bare-Metal Stents in Patients With ST-Segment Elevation Myocardial Infarction: 9-Month Angiographic and Intravascular Ultrasound Results and 12-Month Clinical Outcome: ...Results From the MISSION! Intervention Study Bas L. van der Hoeven, Su-San Liem, J. Wouter Jukema, Navin Suraphakdee, Hein Putter, Jouke Dijkstra, Douwe E. Atsma, Marianne Bootsma, Katja Zeppenfeld, Pranobe V. Oemrawsingh, Ernst E. van der Wall, Martin J. Schalij A randomized study was performed comparing bare-metal stents (BMS) and sirolimus-eluting stents (SES) in 310 ST-segment elevation myocardial infarction patients. Late loss at 9 months was reduced after SES implantation. At 12 months, clinical event rate was lower after SES implantation, mainly due to a reduction in target lesion revascularization. However, late stent malapposition, mostly acquired during the 9-month follow-up period, was more often present after SES implantation, which raises concerns about the long-term risk of stent thrombosis.
Summary Background A microarray-based 70-gene prognosis signature might improve the selection of patients with node-negative breast cancer for adjuvant systemic treatment. The main aims of this ...MicroarRAy PrognoSTics in Breast CancER (RASTER) study were to assess prospectively the feasibility of implementation of the 70-gene prognosis signature in community-based settings and its effect on adjuvant systemic treatment decisions when considered with treatment advice formulated from the Dutch Institute for Healthcare Improvement (CBO) and other guidelines. Methods Between January, 2004 and December, 2006, 812 women aged under 61 years with primary breast carcinoma (clinical T1–4N0M0) were enrolled. Fresh tumour samples were collected in 16 hospitals in the Netherlands within 1 h after surgery. Clinicopathological factors were collected and microarray analysis was done with a custom-designed array chip that assessed the mRNA expression index of the 70 genes previously identified for the prognostic signature. Patients with a “good” signature were deemed to have a good prognosis and, therefore, could be spared adjuvant systemic treatment with its associated adverse effects, whereas patients with a “poor” signature were judged to have a poor prognosis and should be considered for adjuvant systemic treatment. Concordance between risk predicted by the prognosis signature and risk predicted by commonly used clinicopathological guidelines (ie, St Gallen guidelines, Nottingham Prognostic Index, and Adjuvant! Online) was assessed. Findings Of 585 eligible patients, 158 patients were excluded because of sampling failure (n=128) and incorrect procedure (n=30). Prognosis signatures were assessed in 427 patients. The 70-gene prognosis signature identified 219 (51%) patients with good prognosis and 208 (49%) patients with poor prognosis. The Dutch CBO guidelines identified 184 patients (43%) with poor prognosis, which was discordant with those findings obtained with the prognosis signature in 128 (30%) patients. Oncologists recommended adjuvant treatment in 203 (48%) patients based on Dutch CBO guidelines, in 265 (62%) patients if the guidelines were used with the prognosis signature, and in 259 (61%) patients if Dutch CBO guidelines, prognosis signature, and patients' preferences for treatment were all taken into account. Adjuvant! Online guidelines identified more patients with poor prognosis than did the signature alone (294 69%), and discordance with the signature occurred in 160 (37%) patients. St Gallen guidelines identified 353 (83%) patients with poor prognosis with the signature and discordance in 168 (39%) patients. Nottingham Prognostic Index recorded 179 (42%) patients with poor prognosis with the signature and discordance in 117 (27%) patients. Interpretation Use of the prognosis signature is feasible in Dutch community hospitals. Adjuvant systemic treatment was advised less often when the more restrictive Dutch CBO guidelines were used compared with that finally given after use of the prognosis signature. For the other guidelines assessed, less adjuvant chemotherapy would be given when the data based on prognosis signature alone are used, which might spare patients from adverse effects and confirms previous findings. Future studies should assess whether use of the prognosis signature could improve survival or equal survival while avoiding unnecessary adjuvant systemic treatment without affecting patients' survival, and further assess the factors that physicians use to recommend adjuvant systemic treatment.
PDF
