Jonathan Buber

Bloodstream Infections Occurring in Patients With Percutaneously Implanted Bioprosthetic Pulmonary Valve A Single-center Experience

Background—Percutaneous pulmonary valve implantation using a stent-based bioprosthetic valve provides an alternative to surgery in select patients. Systemic infections in Melody valve–implanted patients with and without identified valve involvement have been reported, yet the incidence is unknown, and risk factors remain unidentified. Methods and Results—Between 2007 and 2012, a total of 147 consecutive patients with congenital heart disease underwent Melody percutaneous pulmonary valve implantation at our institution. Demographic and clinical variables were collected at baseline and at follow-up and analyzed as predictors. The occurrence of bloodstream infection (BSI), defined as a bacterial infection treated with ≥4 weeks of antibiotics, served as our primary outcome. The mean age at implantation for the study population was 21.5±11 years, and tetralogy of Fallot was the cardiac condition in 59%. During a median follow-up of 19 months, 14 patients experienced BSI (9.5%; 95% confidence interval, 5.3%–15%). Of these, 4 (2.7%) patients had Melody valve endocarditis. Two patients died during the event, neither of whom had known valve involvement. The median procedure to infection time was 15 months (range, 1–56). In univariate analysis, male sex, previous endocarditis, in situ stents in the right ventricular outflow tract, and presence of outflow tract irregularities at the implant site were associated with BSI occurrence. Conclusions—In this cohort, 9.5% of patients who underwent Melody percutaneous pulmonary valve implantation experienced subsequent BSI, occurring 1 to 56 months after implant, and 2.7% of patients had prosthetic endocarditis. Our findings suggest that patient and nonvalve anatomic factors may be associated with BSI after percutaneous pulmonary valve implantation.

Left Atrial Contractile Function Following a Successful Modified Maze Procedure at Surgery and the Risk for Subsequent Thromboembolic Stroke

OBJECTIVESnThe aim of this study was to evaluate whether certain post-Maze left atrial (LA) contractile profiles may pose a risk for ischemic stroke.nnnBACKGROUNDnThe mechanical contraction of the left atrium may be modified after the Maze procedure. Whether this imposes a risk for stroke, even in the presence of sinus rhythm and after removal of the LA appendage, is not known.nnnMETHODSnClinical, surgery-related, and echocardiographic data from 150 patients who underwent radiofrequency and cryoablation Maze procedures without the use of atrial incisions between 2004 and 2009 and were in sustained sinus rhythm were collected and analyzed. The occurrence of stroke was evaluated by reviewing clinical records. All stroke events were adjudicated by a neurologist.nnnRESULTSnAt a mean follow-up time of 24.5 months, 15 patients (10%) had experienced ischemic strokes. Forty-seven patients (31%) had no evidence of LA mechanical contraction at 3 months after surgery (baseline assessment) and on follow-up echocardiography. Multivariate analysis showed that a lack of LA mechanical contraction at baseline was associated with a 5-fold increase in the risk for stroke (p = 0.02) during follow-up. Larger atria imposed a significant risk as well; LA volume index ≥33 ml/m(2) was associated with a 3-fold risk increase (p = 0.03). These effects were maintained regardless of the lack of mechanical valve implantation and anticoagulation treatment.nnnCONCLUSIONSnAbsence of LA contraction and LA volume index ≥33 ml/m(2) result in a significant increase in the risk for thromboembolic stroke after the Maze procedure for patients in sinus rhythm.

Risk of Recurrent Cardiac Events After Onset of Menopause in Women With Congenital Long-QT Syndrome Types 1 and 2

Background— Women with congenital long-QT syndrome experience an increased risk for cardiac events after the onset of adolescence that is more pronounced among carriers of the LQT2 genotype. We hypothesized that the hormonal changes associated with menopause may affect clinical risk in this population. Methods and Results— We used a repeated-events analysis to evaluate the risk for recurrent syncope during the menopause transition and postmenopausal periods (5 years before and after the age at onset of menopause, respectively) among 282 LQT1 (n=151) and LQT2 (n=131) women enrolled in the Long-QT Syndrome Registry. Multivariate analysis showed that the risk for recurrent syncope (n=150) among LQT2 women was significantly increased during both menopause transition (hazard ratio, 3.38; P=0.005) and the postmenopausal period (hazard ratio, 8.10; P<0.001) compared with the reproductive period. The risk increase was evident among women who did or did not receive estrogen therapy. In contrast, among LQT1 women, the onset of menopause was associated with a reduction in the risk for recurrent syncope (hazard ratio, 0.19; P=0.05; P=0.02 for genotype-by-menopause interaction). Only 22 women (8%) experienced aborted cardiac arrest or sudden cardiac death during follow-up. The frequency of aborted cardiac arrest/sudden cardiac death showed a similar genotype-specific association with the onset of menopause. Conclusions— The onset of menopause is associated with a significant increase in the risk of cardiac events (dominated by recurrent episodes of syncope) in LQT2 women, suggesting that careful follow-up and continued long-term therapy are warranted in this population.

Wearable Defibrillator in Congenital Structural Heart Disease and Inherited Arrhythmias

Patients with congenital structural heart disease (CSHD) and inherited arrhythmias (IAs) are at high risk of ventricular tachyarrhythmias and sudden cardiac death. The present study was designed to evaluate the short- and long-term outcomes of patients with CSHD and IA who received a wearable cardioverter-defibrillator (WCD) for the prevention of sudden cardiac death. The study population included 162 patients with CSHD (n = 43) and IA (n = 119) who were prospectively followed up in a nationwide registry from 2005 to 2010. The mortality rates were compared using Kaplan-Meier survival analysis. The mean age of the study patients was 38 ± 27 years. The patients with CSHD had a greater frequency of left ventricular dysfunction (ejection fraction <30%) than did the patients with IA (37% vs 5%, respectively; p = 0.002). The predominant indication for WCD was pending genetic testing in the IA group and transplant listing in the CSHD group. Compliance with the WCD was similar in the 2 groups (91%). WCD shocks successfully terminated 3 ventricular tachyarrhythmias in the patients with IA during a median follow-up of 29 days of therapy (corresponding to 23 appropriate WCD shocks per 100 patient-years). No arrhythmias occurred in the patients with CSHD during a median follow-up of 27 days. No patients died while actively wearing the WCD. At 1 year of follow-up, the survival rates were significantly lower among the patients with CSHD (87%) than among the patients with IA (97%, p = 0.02). In conclusion, our data suggest that the WCD can be safely used in high-risk adult patients with IA and CSHD. Patients with IA showed a greater rate of ventricular tachyarrhythmias during therapy but significantly lower long-term mortality rates.

Reduction in Life-Threatening Ventricular Tachyarrhythmias in Statin-Treated Patients With Nonischemic Cardiomyopathy Enrolled in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy)

OBJECTIVESnThis study hypothesized that time-dependent statin therapy will reduce the risk of life-threatening ventricular tachyarrhythmias among patients with nonischemic cardiomyopathy (NICM) enrolled in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy).nnnBACKGROUNDnPrior studies suggested that statin therapy exerts antiarrhythmic properties among patients with coronary artery disease. However, data regarding the effect of statins on arrhythmic risk among patients with NICM are limited.nnnMETHODSnMultivariate Cox proportional hazards regression modeling was used to assess the effect of statin therapy, evaluated as a time-dependent covariate, on the risk of appropriate defibrillator therapy for fast ventricular tachycardia (VT) (defined as a rate faster than 180 beats/min)/ventricular fibrillation (VF) or death (primary endpoint) and appropriate defibrillator shocks (secondary endpoint) among 821 patients with NICM enrolled in the MADIT-CRT trial.nnnRESULTSnStatin users (n = 499) were older and had a higher prevalence of diabetes and hypertension yet were less frequently smokers. Multivariate analysis showed that time-dependent statin therapy was independently associated with a significant 77% reduction in the risk of fast VT/VF or death (p < 0.001) and with a significant 46% reduction in the risk of appropriate implantable cardioverter defibrillator shocks (p = 0.01). Consistent with these findings, the cumulative probability of fast VT/VF or death at 4 years of follow-up was significantly lower among patients who were treated with statins (11%) as compared with study patients who were not treated with statins (19%; p = 0.006 for the overall difference during follow-up).nnnCONCLUSIONSnStatin use was associated with a significant reduction in the risk of life-threatening ventricular tachyarrhythmias among patients with NICM.

Predictors and outcomes of "super-response" to cardiac resynchronization therapy

BACKGROUNDnCardiac resynchronization therapy (CRT) has been shown to improve heart failure (HF) symptoms and survival. We hypothesized that a greater improvement in left-ventricular ejection fraction (LVEF) after CRT is associated with greater survival benefit.nnnMETHODS AND RESULTSnIn 693 patients across 2 international centers, the improvement in LVEF after CRT was determined. Patients were grouped as non-/modest-, moderate-, or super-responders to CRT, defined as an absolute change in LVEF of ≤5%, 6-15%, and >15%, respectively. Changes in New York Heart Association (NYHA) functional class and left ventricular end-diastolic dimension (LVEDD) were assessed for each group. There were 395 non-/modest-, 186 moderate-, and 112 super-responders. Super-responders were more likely to be female and to have nonischemic cardiomyopathy, lower creatinine, and lower pulmonary artery systolic pressure than non-/modest- and moderate-responders. Super-responders were also more likely to have lower LVEF than non-/modest-responders. There was no difference in NYHA functional class, mitral regurgitation grade, or tricuspid regurgitation grade between groups. Improvement in NYHA functional class (-0.9xa0±xa00.9 vs -0.4xa0±xa00.8 [Pxa0<xa0.001] and -0.6xa0±xa00.8 [Pxa0=xa0.02]) and LVEDD (-8.7xa0±xa09.9xa0mm vs -0.5xa0±xa05.0 and -2.4xa0±xa05.8xa0mm [Pxa0<xa0.001 for both]) was greatest in super-responders. Kaplan-Meier survival analysis revealed that super-responders achieved better survival compared with non-/modest- (Pxa0<xa0.001) and moderate-responders (Pxa0=xa0.049).nnnCONCLUSIONSnImprovement in HF symptoms and survival after CRT is proportionate to the degree of improvement in LV systolic function. Super-response is more likely in women, those with nonischemic substrate, and those with lower pulmonary artery systolic pressure.

Durability of large diameter right ventricular outflow tract conduits in adults with congenital heart disease

BACKGROUNDnSubpulmonary ventricular outflow conduits are utilized routinely to repair complex congenital cardiac abnormalities, but are limited by the inevitable degeneration and need for reintervention. Data on conduit durability and propensity to dysfunction in the adult population are limited.nnnMETHODSnThe study included 288 consecutive patients ≥18 years of age who were evaluated between 1991 and 2010 after placement of a ≥18 mm conduit. Freedom from hemodynamic conduit dysfunction served as our primary outcome. Freedom from reintervention, overall mortality and heart transplantation were also evaluated.nnnRESULTSnMedian age at conduit implant was 19 years and median follow-up duration was 13 years. Probabilities of survival without conduit dysfunction and reintervention at 5, 10 and 15 years were 87%, 63%, and 49%, and 95%, 81%, and 56%, respectively. Smaller conduit diameter (18-20mm) was associated with lower probability of survival without dysfunction in the entire study cohort, with prominent effects in patients in both the lowest and the highest age quartiles. Other parameters with similar associations were higher BMI, native anatomy of tetralogy of Fallot or truncus arteriosus, and active smoking.nnnCONCLUSIONSnAdult congenital heart disease patients with conduit diameter ≥18 mm had an approximately 50% chance of developing hemodynamic conduit dysfunction and undergoing conduit reintervention by 15 years of post-implant, and a 30% likelihood of undergoing conduit reoperation in the same time frame. The importance of these data is underscored by the increasing number of adults with congenital heart diseases seeking care and the recent advances in transcatheter valve replacement for dysfunctional conduits.

Genotype-specific QT correction for heart rate and the risk of life-threatening cardiac events in adolescents with congenital long-QT syndrome

BACKGROUNDnA prolonged QT interval corrected for heart rate (QTc) is a major risk factor in patients with long QT syndrome (LQTS). However, heart rate-related risk in this genetic disorder differs among genotypes.nnnOBJECTIVEnThis study hypothesized that risk assessment in LQTS patients should incorporate genotype-specific QT correction for heart rate.nnnMETHODSnThe independent contribution of 4 repolarization measures (the absolute QT interval, and Bazetts, Fridericias, and Framinghams correction formulas) to the risk of aborted cardiac arrest or sudden cardiac death during adolescence, before and after further adjustment for the RR interval, was assessed in 727 LQTS type 1 and 582 LQTS type 2 patients. Improved QT/RR correction was calculated using a Cox model, dividing the coefficient on log(RR) by that on log(QT).nnnRESULTSnMultivariate analysis demonstrated that in LQTS type 1 patients 100-ms increments in the absolute QT interval were associated with a 3.3-fold increase in the risk of life-threatening cardiac events (P = .020), and 100-ms decrements in the RR interval were associated with a further 1.9-fold increase in the risk (P = .007), whereas in LQTS type 2 patients, resting heart rate was not a significant risk factor (hazard ratio 1.11; P = .51; P value for heart rate × genotype interaction = .036). Accordingly, analysis of an improved QT correction formula showed that patients with the LQTS type 1 genotype required a greater degree of QT correction for heart rate (improved QTc = QT/RR⁰·⁸) than LQTS type 2 patients (improved QTc = QT/RR⁰·²).nnnCONCLUSIONnOur findings suggest that risk stratification for life-threatening cardiac events in LQTS patients can be improved by incorporating genotype-specific QT correction for heart rate.

Clinical course and outcome of patients enrolled in US and non-US centres in MADIT-CRT

AIMSnWe aimed to evaluate within the MADIT-CRT database whether different enrollment characteristics between US and non-US centres affected the clinical course of study patients.nnnMETHODS AND RESULTSnWe evaluated differences in baseline characteristics, procedure-associated complications, clinical as well as echocardiographic response to cardiac resynchronization therapy with a defibrillator (CRT-D), between patients enrolled in 87 US centres (n = 1271) and 23 non-US centres (n = 549) in MADIT-CRT. Non-US patients displayed significant differences in baseline characteristics from US patients, including a higher frequency of left bundle branch block, a more advanced heart failure (HF) functional class >3 months prior to enrollment, and larger baseline cardiac volumes. Procedure-related complications occurred at a significantly higher frequency among patients enrolled in non-US centres (17%) than among those enrolled in US centres (10%; P < 0.001). During follow-up, CRT-D was associated with 42% (P = 0.003) and 38% (P < 0.001) reductions in the risk of HF or death in the two respective groups (P for the difference = 0.80), and with similar reductions in cardiac volumes (all P > 0.10). Subgroup analysis showed a more pronounced effect of CRT-D among women in the US group, including a significant 71% (P = 0.02) reduction in the risk of death, whereas CRT-D therapy was associated with a significant clinical benefit in men only in the non-US group.nnnCONCLUSIONnPatients enrolled in US and non-US centres in MADIT-CRT displayed significant differences in baseline clinical and echocardiographic characteristics and in the frequency of procedure-related complications, but experienced an overall similar clinical and echocardiographic response to CRT-D.

Effects of tricuspid valve regurgitation on clinical and echocardiographic outcome in patients with cardiac resynchronization therapy

AIMSnThe severity of tricuspid regurgitation (TR) is a predictor of outcome among heart failure patients. The interaction between cardiac resynchronization therapy (CRT) and TR has not been described. In this study, we examined the effect of pre-implant TR, and worsened TR post-implant, on response to CRT and overall survival.nnnMETHODS AND RESULTSnWe included all patients with successfully implanted CRT systems between 2007 and 2010. Patients were divided into two groups pre-implant: (Gp 1) no-or-mild TR; and (Gp 2) moderate-or-severe TR. Post-implant, patients were divided into two groups: (Gp A) improved or stable TR; and (Gp B) worsened TR. The clinical and echocardiographic outcome of all patients was assessed. The study included 193 patients. Thirty-five subjects (18%) had moderate or severe TR pre-implant (Gp 2). Baseline echo parameters and 6 min walk distance were worse in Gp 2 compared with Gp 1 (mild or no TR). There was no significant difference in clinical response to CRT between the two groups. However, Gp 2 had a significantly lower echocardiographic response (35 vs. 60%, P = 0.01) and higher mortality over 3 years (OR = 6.70, 95% CI = 1.8-24.5, P = 0.004). Post-implant, 25 patients (13%) developed worsened TR (Gp B), not associated with deterioration in right ventricle function or elevation in pulmonary artery pressure. Worsened TR predicted a reduced clinical response to CRT (42 vs. 70%, P = 0.006), when compared with Gp A.nnnCONCLUSIONSnThe presence of baseline moderate or severe TR is associated with increased mortality but does not predict clinical or echocardiographic response to CRT. Patients with worsened TR following CRT are less likely to clinically respond to CRT. Pacing leads passing through the tricuspid valve may worsen TR. It is conceivable that avoidance of lead-induced TR by alternative implantation techniques could improve the response rate to CRT.