Although the implantable cardioverter-defibrillator (ICD) remains the main therapy for Brugada syndrome (BrS), it does not reduce life-threatening ventricular arrhythmia. Based on pathophysiologic ...mechanisms, hydroquinidine (HQ) has been suggested for effective prevention of arrhythmia.
The purpose of this study was to provide evidence-based data supporting HQ use to prevent life-threatening ventricular arrhythmia in high-risk patients with BrS.
We performed a prospective multicenter randomized (HQ vs placebo) double-blind study with two 18-month crossover phases in patients with BrS and implanted with an ICD.
Among the 50 patients enrolled (mean age 47.0 ± 11.4 years, 42 84% male), 26 (52%) fully completed both phases. Thirty-four (68%) presented HQ-related side effects, mainly gastrointestinal, which led to discontinuation of the therapy in 13 (26%). HQ lengthened the QTc interval (409 ± 32 ms vs 433 ± 37 ms; P = .027) and increased repolarization dispersion as evaluated by Tpe max in precordial leads (89 ± 15 ms vs 108 ± 27 ms; P <.0001) with no significant changes in J-point elevation. During the 36-month follow-up, 1 appropriate ICD shock (0.97% event per year), 1 self-terminating ventricular fibrillation, and 1 inappropriate ICD shock occurred under placebo therapy. No arrhythmic events were reported under HQ therapy.
Although HQ seems to be effective in preventing life-threatening ventricular arrhythmia, it could not be an alternative for ICD implantation. Its frequent side effects greatly reduce its probable compliance and therefore do not reveal a significant effect. HQ increases repolarization dispersal with no changes in BrS pattern, which could indicate a more complex action of HQ than its I
blocking effect alone.
Programming implantable cardioverter-defibrillators (ICDs) with a high-rate therapy strategy has proven to be effective in reducing shocks and is associated with a reduced mortality.
We sought to ...determine the impact of a very high rate cutoff programming strategy on outcomes in patients with a primary indication for an ICD due to reduced left ventricular ejection fraction.
Using data from the multicenter French DAI-PP registry, this cohort-controlled study compared outcomes in 500 patients programmed with a very high rate cutoff (VH-RATE group: monitor zone 170-219 beats/min; ventricular fibrillation zone ≥220 beats/min with 13 ± 4 detection intervals) with 1500 matched control patients programmed with 1 or 2 therapy zone. All ICDs were implanted for primary prevention in patients with systolic dysfunction. Risks of events were compared after propensity score matching of sex, age, ejection fraction, New York Heart Association class, cardiomyopathy, atrial fibrillation, and type of device.
After a mean follow-up of 3.6 ± 2.3 years, VH-RATE programming was associated with a reduction of appropriate therapy risk (hazard ratio HR 0.40; 95% confidence interval CI 0.31-0.51; P < .0001) and inappropriate shock (HR 0.42; 95% CI 0.27-0.63; P < .0001). It was also associated with a decreased risk of sudden cardiac death (HR 0.43; 95% CI 0.17-0.99; P = .04) as compared with patients programmed with 2 therapy zones. There was no significant difference in overall survival between the groups.
In patients implanted with an ICD in primary prevention with left ventricular dysfunction, very high rate cutoff programming (single therapy zone ≥220 beats/min) was associated with a 60% reduction of appropriate therapies as well as inappropriate shocks, without affecting mortality.
The lifesaving benefit of implantable cardioverter-defibrillators (ICDs) has been demonstrated. Their use has increased considerably in the past decade, but related complications have become a major ...concern.
The purpose of this study was to assess the incidence and effect on outcomes of early (≤30 days) complications after ICD implantation for primary prevention in a large French population.
We analyzed data from 5539 patients from the multicenter French DAI-PP (Défibrillateur Automatique Implantable-Prévention Primaire) registry (2002-2012) who had coronary artery disease or dilated cardiomyopathy and were implanted with an ICD for primary prevention.
Overall, early complications occurred in 707 patients (13.5%), mainly related to lead dislodgment or hematoma (57%). Independent factors associated with occurrence of early complications were severe renal impairment (odds ratio OR 1.66, 95% confidence interval CI 1.17-2.37, P = .02), age ≥75 years (OR 1.01, 95% CI 1.00-1.02, P = .03), cardiac resynchronization therapy (OR 1.58, 95% CI 1.16-2.17, P = .01), and anticoagulant therapy (OR 1.28, 95% CI 1.02-1.61, P = .03). During a mean ± SD follow-up of 3.1 ± 2.3 years, 824 (15.8%) patients experienced ≥1 late complication (>30 days), and 782 (14.9%) patients died. After adjustment, early complications remained associated with occurrence of late complications (OR 2.15, 95% CI 1.73-2.66, P < .0001) and mortality (OR 1.70, 95% CI 1.34-2.17, P = .003).
Early complications are common after ICD implantation for primary prevention, occurring in 1 in 7 patients, and are associated with an increased risk of late complications and overall mortality. Further studies are needed to investigate the underlying mechanisms of such associations.
Abstract We aimed to assess if the outcome of primary prevention implantable cardioverter defibrillators (ICDs) without cardiac resynchronization therapy (CRT) is dependent on New York Heart ...Association (NYHA) class. Among the participants of Défibrillateur Automatique Implantable-Prévention Primaire (DAI-PP;NCT01992458) multicenter cohort study, 155 patients in NYHA class I, 504 in NYHA class II and 188 in NYHA class III had a QRS width <120ms and were implanted with an ICD without CRT, and thus were eligible for the purpose of this analysis. Total and specific mortalities, and the incidence of appropriate therapies were assessed for every NYHA. During 2,606 patient-years (3.1±2.1 years), 104 (12.3%) individuals died and 188 (22.2%) experienced appropriate therapies. After adjustment, overall mortality increased with NYHA class (adjusted HR=1.63, 95%CI 1.11-2.41, P=0.014), driven by an increase in cardiovascular death. Conversely, incidence of appropriate ICD intervention was comparable among the 3 NYHA groups (NYHA class I 7.43, NYHA class II 7.91 and NYHA class III 12.10 per 100 patient-years; HR=1.19, 95%CI 0.89-1.59, P=0.231). Incidence of ICD-unresponsive sudden death was very low and also comparable (NYHA class I 0.22, NYHA class II 0.36, and NYHA class III 0.83 per 100 patient-years; (HR=6.34, 95%CI 0.32-124.49, P=0.224). No significant differences were observed in the other specific modes of death. In conclusion, even though patients in NYHA class III have higher overall mortality, they experience a comparable incidence of appropriate ICD therapies. The low incidence of ICD-unresponsive sudden death in all assessed NYHA classes also supports the efficacy of ICDs, irrespective of NYHA class.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract Background The early repolarization (ER) pattern is associated with an increased risk of arrhythmogenic sudden death. However, strategies for risk stratification of patients with the ER ...pattern are not fully defined. Objectives This study sought to determine the role of electrophysiology studies (EPS) in risk stratification of patients with ER syndrome. Methods In a multicenter study, 81 patients with ER syndrome (age 36 ± 13 years, 60 males) and aborted sudden death due to ventricular fibrillation (VF) were included. EPS were performed following the index VF episode using a standard protocol. Inducibility was defined by the provocation of sustained VF. Patients were followed up by serial implantable cardioverter-defibrillator interrogations. Results Despite a recent history of aborted sudden death, VF was inducible in only 18 of 81 (22%) patients. During follow-up of 7.0 ± 4.9 years, 6 of 18 (33%) patients with inducible VF during EPS experienced VF recurrences, whereas 21 of 63 (33%) patients who were noninducible experienced recurrent VF (p = 0.93). VF storm occurred in 3 patients from the inducible VF group and in 4 patients in the noninducible group. VF inducibility was not associated with maximum J-wave amplitude (VF inducible vs. VF noninducible; 0.23 ± 0.11 mV vs. 0.21 ± 0.11 mV; p = 0.42) or J-wave distribution (inferior, odds ratio OR: 0.96 95% confidence interval (CI): 0.33 to 2.81; p = 0.95; lateral, OR: 1.57 95% CI: 0.35 to 7.04; p = 0.56; inferior and lateral, OR: 0.83 95% CI: 0.27 to 2.55; p = 0.74), which have previously been demonstrated to predict outcome in patients with an ER pattern. Conclusions Our findings indicate that current programmed stimulation protocols do not enhance risk stratification in ER syndrome.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Short QT syndrome is associated with an increased risk of cardiac arrhythmias and unexpected sudden death. Until now, only mutations in genes encoding the cardiac potassium and calcium channels have ...been implicated in early T-wave repolarization.
The purpose of this study was to confirm a relationship between a short QT syndrome and carnitine deficiency.
We report 3 patients affected by primary systemic carnitine deficiency and an associated short QT syndrome. Ventricular fibrillation during early adulthood was the initial symptom in 1 case. To confirm the relationship between carnitine, short QT syndrome, and arrhythmias, we used a mouse model of carnitine deficiency induced by long-term subcutaneous perfusion of MET88.
MET88-treated mice developed cardiac hypertrophy associated with a remodeling of the mitochondrial network. The continuous monitoring of electrocardiograms confirmed a shortening of the QT interval, which was negatively correlated with the plasma carnitine concentration. As in humans, such alterations coincided with the genesis of ventricular premature beats and ventricular tachycardia and fibrillation.
Altogether, these results suggest that long-chain fatty acid metabolism influence the morphology and the electrical function of the heart.
Because all the data in this study were obtained retrospectively, the completeness and accuracy of the collection into the database may not be optimal. Overall, of the risk stratification schemas for ...EC in patients with infective endocarditis, the French and the Italian scoring systems had moderate predictive power, but the Italian scheme may offer better predictive capacity and may be simpler to apply. References 1 L. Pericart, L. Fauchier, T. Bourguignon, Long-term outcome and valve...
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Objectives The objective of this study was to investigate the feasibility of identifying heart failure patients who are less likely to benefit from implantable cardioverter-defibrillator ...(ICD) therapy among those eligible for primary prevention ICDs. Background The cost-effectiveness of ICDs in primary prevention may be improved dramatically. Methods Using a cause-of-death analysis approach, we evaluated the discriminative and predictive values of a risk score with regard to overall mortality and specific causes of death by examining 2,485 patients enrolled in the French Primary Prevention ICD program (2002 to 2012). The risk score included points for New York Heart Association functional class III or greater, age >70 years, QRS duration >120 ms, atrial fibrillation, and glomerular filtration rate <60 ml/min. Sensitivity analyses were performed for ischemic and nonischemic cardiomyopathy, as well as for patients undergoing cardiac resynchronization therapy. Results After a mean follow-up of 3.0 ± 2.1 years, the overall mortality rate was 5.9 per 100 patient-years (95% confidence interval: 5.4 to 6.5), which increased with the number of risk factors (0 to 5, respectively), as follows: 2.5, 2.9, 4.8, 9.0, 12.3, and 14.8 per 100 patient-years (p < 0.001). The higher mortality rate among patients with the highest scores resulted from an increase in nonarrhythmic mortality (from 2.1 to 14.8 per 100 patient-years, p < 0.001), whereas the occurrence of appropriate ICD therapies did not change significantly across the categories. The C statistic testing of the score was observed to be highly similar for patients with ischemic cardiomyopathy (0.685) and nonischemic cardiomyopathy (0.658) and those receiving cardiac resynchronization therapy (0.678). Conclusions Our findings suggest the feasibility of and interest in identifying patients eligible for primary prevention ICD implantation who are at significant risk of nonarrhythmic death in the real-world setting.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Background Atrial fibrillation is the most common cardiac complication of hyperthyroidism. The association between history of hyperthyroidism and stroke remains unclear. We sought to ...determine whether history of thyroid dysfunction is a thromboembolic risk factor in patients with atrial fibrillation. Methods Patients with atrial fibrillation seen in an academic institution between 2000 and 2010 were identified and followed-up. Clinical events (stroke/systemic embolism, bleeding, all-cause death) were recorded and related to thyroid status and disorders. Associations were examined in time-dependent models with adjustment for relevant confounders. Results Among 8962 patients, 141 patients had a history of hyperthyroidism, 540 had a history of hypothyroidism, and 8271 had no thyroid dysfunction. Mean follow-up was 929 ± 1082 days. A total of 715 strokes/systemic embolism were recorded, with no significant difference in the rates of these events in patients with a history of thyroid dysfunction vs those without thyroid problems in either univariate or multivariable analysis (hazard ratio HR 0.85; 95% confidence interval CI, 0.41-1.76 for hyperthyroidism; HR 0.98; 95% CI, 0.73-1.34 for hypothyroidism). There were 791 bleeding events; history of hypothyroidism was independently related to a higher rate of bleeding events (HR 1.35; 95% CI, 1.02-1.79). No significant difference among the 3 groups was observed for the incidence of death. Conclusions History of hyperthyroidism was not an independent risk factor for stroke/systemic embolism in atrial fibrillation, whereas hypothyroidism was associated with a higher risk of bleeding events. These data suggest no additional benefit from the inclusion of thyroid dysfunction in thromboembolic prediction models in atrial fibrillation.
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