Objectives The present study was designed to explore the 8-year survival benefit of a nonresynchronization implantable cardioverter-defibrillator (ICD) according to a simple risk stratification ...score. Background There is limited information regarding factors that predict the benefit of primary prevention with an ICD during long-term follow-up. Methods This study used a previously developed risk score including 5 clinical factors (New York Heart Association functional class >II, age >70 years, blood urea nitrogen >26 mg/dl, QRS duration >0.12 s, and atrial fibrillation) to evaluate 8-year ICD survival benefit within risk score categories among 1,191 MADIT-II (Multicenter Automatic Defibrillator Implantation Trial II) patients. Results Patients with low (0 risk factors, n = 345) and intermediate risk (1 to 2 risk factors, n = 646) demonstrated a significantly higher probability of survival at 8-year follow-up when treated by ICD as compared with non-ICD therapy (75% vs. 58%, p = 0.004; and 47% vs. 31%, p < 0.001, respectively). By contrast, among high-risk patients (3 or more risk factors, n = 200), there was no significant difference in 8-year survival between the ICD and non-ICD subgroups (19% vs. 17%, p = 0.50). Consistently, multivariate analysis showed that ICD therapy was associated with a significant long-term survival benefit among low- and intermediate-risk patients (hazard ratio HR: 0.52, p < 0.001, and HR: 0.66, p < 0.001, respectively), whereas treatment with an ICD was not associated with a significant benefit among high-risk patients (HR: 0.84, p = 0.25). Conclusions These findings suggest that a simple risk score can identify patients who derive significant long-term benefit from primary ICD therapy. High-risk patients with multiple comorbidities composed 17% of the MADIT-II population and did not derive long-term benefit from nonresynchronization device therapy.
Objectives We aimed to evaluate the relationship between echocardiographic response to cardiac resynchronization therapy (CRT) and the risk of subsequent ventricular tachyarrhythmias (VTAs). ...Background Current data regarding the effect of CRT on the risk of VTA are limited and conflicting. Methods The risk of a first appropriate implantable cardioverter-defibrillator (ICD) therapy for VTA (including ventricular tachycardia, ventricular fibrillation, and ventricular flutter) was compared between high- and low-echocardiographic responders to CRT defibrillator (CRT-D) therapy (defined as ≥25% and <25% reductions, respectively, in left ventricular end-systolic volume LVESV at 1 year compared with baseline) and ICD-only patients enrolled in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy). Results The cumulative probability of a first VTA at 2 years after assessment of echocardiographic response was highest among low responders to CRT-D (28%), intermediate among ICD-only patients (21%), and lowest among high responders to CRT-D (12%), with p < 0.001 for the overall difference during follow-up. Multivariate analysis showed that high responders to CRT-D experienced a significant 55% reduction in the risk of VTA compared with ICD-only patients (p < 0.001), whereas the risk of VTA was not significantly different between low responders and ICD-only patients (hazard ratio HR: 1.26; p = 0.21). Consistently, assessment of response to CRT-D as a continuous measure showed that incremental 10% reductions in left ventricular end-systolic volume were associated with corresponding reductions in the risk of subsequent VTA (HR: 0.80; p < 0.001), VTA/death (HR: 0.79; p < 0.001), ventricular tachycardia (HR: 0.80; p < 0.001), and ventricular fibrillation/ventricular flutter (HR: 0.75; p = 0.044). Conclusions In patients with left ventricular dysfunction enrolled in the MADIT-CRT trial, reverse remodeling was associated with a significant reduction in the risk of subsequent life-threatening VTAs. (Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy MADIT-CRT; NCT00180271 )
An important determinant of successful cardiac resynchronization therapy for heart failure is the position of the left ventricular (LV) pacing lead. The aim of this study was to analyze the impact of ...the LV lead position on outcome in patients randomized to cardiac resynchronization-defibrillation in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT) study.
The location of the LV lead was assessed by means of coronary venograms and chest x-rays recorded at the time of device implantation. The LV lead location was classified along the short axis into an anterior, lateral, or posterior position and along the long axis into a basal, midventricular, or apical region. The primary end point of MADIT-CRT was heart failure (HF) hospitalization or death, whichever came first. The LV lead position was assessed in 799 patients, (55% patients ≥65 years of age, 26% female, 10% LV ejection fraction ≤25%, 55% ischemic cardiomyopathy, and 71% left bundle-branch block) with a follow-up of 29±11 months. The extent of cardiac resynchronization therapy benefit was similar for leads in the anterior, lateral, or posterior position (P=0.652). The apical lead location compared with leads located in the nonapical position (basal or midventricular region) was associated with a significantly increased risk for heart failure/death (hazard ratio=1.72; 95% confidence interval, 1.09 to 2.71; P=0.019) after adjustment for the clinical covariates. The apical lead position was also associated with an increased risk for death (hazard ratio=2.91; 95% confidence interval, 1.42 to 5.97; P=0.004).
LV leads positioned in the apical region were associated with an unfavorable outcome, suggesting that this lead location should be avoided in cardiac resynchronization therapy. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique identifier: NCT00180271.
Intermediate- or low-risk patients with severe aortic stenosis were excluded from earlier transcatheter aortic valve implantation (TAVI) clinical trials; however, they are already being treated by ...TAVI despite a lack of data regarding the safety and efficacy in these patients. We aimed to assess the safety and efficacy of TAVI in patients at intermediate or low risk. Patients undergoing TAVI during 2008 to 2014 were included into a shared database (n = 1,327). Procedural outcomes were adjudicated according to Valve Academic Research Consortium 2 definitions. Patients were stratified according to their Society of Thoracic Surgeons (STS) score into 3 groups: high (STS ≥8, n = 223, 17%), intermediate (STS 4 to 8; n = 496, 38%), or low risk (STS <4; n = 576, 45%). Low-risk patients were significantly younger and more likely to be men compared to intermediate- and high-risk patients. Baseline characteristics differed significantly between the groups with a gradual increase in the rates of previous bypass surgery, stroke, peripheral vascular disease, renal failure, lung disease, and frailty scores, from low to high risk groups. Compared with intermediate- and high-risk patients, low-risk patients were more likely to undergo TAVI through the transfemoral route (81% vs 88% vs 95%, p <0.001) and under conscious sedation (69% vs 72% vs 81%, <0.001). There were no significant differences in the rates of procedural complications apart from acute kidney injury (19% vs 17% vs 13%, p = 0.03) and stroke rates (4.5% vs 2% vs 2.3%, p = 0.1). Short- and long-term mortality rates were significantly higher for intermediate- (hazard ratio HR 1.9, 95% confidence interval CI 1.2 to 2.9) and high-risk patients (HR 4.1, 95% CI 2.7 to 6.4) than low-risk patients also after multivariate adjustment (HR 1.6, 95% CI 1 to 2.6 and HR 2.7, 95% CI 1.7 to 4.5, respectively; all p <0.05). In conclusion, TAVI for intermediate- and low-risk patients is safe and associated with improved outcome compared with high-risk patients.
Objectives This study aimed to evaluate the effect of cardiac resynchronization therapy with a defibrillator (CRT-D) on the risks of first and recurrent ventricular tachyarrhythmic events (VTEs) in ...the MADIT-CRT. Background Reverse remodeling associated with CRT-D therapy was suggested to reduce arrhythmic risk. However, the effect of the device on the risk of recurrent VTEs among patients who experience a first arrhythmic event has not been investigated. Methods The CRT-D versus defibrillator-only risks for first and subsequent fast VTEs (>180 beats/min) were assessed by Cox proportional hazards and Andersen-Gill proportional intensity regression modeling, respectively, in efficacy analyses recognizing active device-type during follow-up. Results Multivariate analysis showed that CRT-D was associated with a significant 29% (p = 0.003) reduction in the risk of a first VTE, with a pronounced effect among patients with left bundle branch block (LBBB) (hazard ratio HR: 0.58; p < 0.001) and no significant effect among non-LBBB patients (HR: 1.05; p = 0.82, p for the difference = 0.02). Patients with LBBB who experienced a first VTE had no change in the risk of subsequent VTEs with CRT-D (HR: 0.98; p = 0.85). In contrast, the risk of recurrent VTEs with CRT-D was significantly increased among non-LBBB patients (HR: 3.62; p = 0.002, p for the difference = 0.009). Recurrent VTEs increased the risk of subsequent heart failure or death. Conclusions In MADIT-CRT, active treatment with CRT-D was associated with a significant reduction in the risk of life-threatening VTEs. However, our findings suggest that CRT-D does not reduce the risk of subsequent VTEs in patients who experience a first arrhythmic event and may increase subsequent arrhythmic risk in non-LBBB patients. (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy MADIT-CRT; NCT00180271 )
The extent of myocardial fibrosis in patients with severe aortic stenosis might have an important prognostic value. Non-invasive imaging to quantify myocardial fibrosis by measuring extracellular ...volume fraction might have an important clinical utility prior to aortic valve intervention.
Seventy-five consecutive patients with severe aortic stenosis, and 19 normal subjects were prospectively recruited and underwent pre- and post-contrast computed tomography for estimating myocardial extracellular volume fraction. Serum level of galectin-3 was measured and 2-dimensional echocardiography was performed to characterize the extent of cardiac damage using a recently published aortic stenosis staging classification.
Extracellular volume fraction was higher in patients with aortic stenosis compared to normal subjects (40.0±11% vs. 21.6±5.6%; respectively, p<0.001). In patients with aortic stenosis, extracellular volume fraction correlated with markers of left ventricular decompensation including New York Heart Association functional class, left atrial volume, staging classification of aortic stenosis and lower left ventricular ejection fraction. Out of 75 patients in the AS group, 49 underwent TAVI, 6 surgical AVR, 2 balloon valvuloplasty, and 18 did not undergo any type of intervention. At 12-months after aortic valve intervention, extracellular volume fraction predicted the combined outcomes of stroke and hospitalization for heart failure with an area under the curve of 0.77 (95% confidence interval: 0.65-0.88). A trend for correlation between serum galectin-3 and extracellular volume was noted.
In patients with severe aortic stenosis undergoing computed tomography before aortic valve intervention, quantification of extracellular volume fraction correlated with functional status and markers of left ventricular decompensation, and predicted the 12-months composite adverse clinical outcomes. Implementation of this novel technique might aid in the risk stratification process before aortic valve interventions.
Abstract Patients with advanced chronic renal dysfunction were excluded from randomized trials of transcatheter aortic valve replacement (TAVR). The potential impact of chronic renal disease on TAVR ...prognosis is not fully understood. We aim to evaluate outcomes within a large cohort of patients undergoing TAVR distinguished by renal function. Baseline characteristics, procedural data and clinical follow-up findings were collected from 10 high-volume TAVR centers in Europe, Israel and Japan. Data was analyzed according to renal function. Patients (n=1204) were divided into 4 groups according to pre-TAVR estimated glomerular filtration rate (eGFR): group I (eGFR >60) n=288 (female 45%), group II (eGFR 31-60) n=452 (female 61%), group III (eGFR ≤30) n=398 (female 61%) and group IV (dialysis) n=66 (female 31%). Mean Society of Thoracic Surgeons (STS) score was higher in patients with lower pre-procedural eGFR. All-cause mortality at 1-year was higher in patients with lower eGFR (9.0%, 12.1%, 24.3%, 24.2% for group I, II, III and IV; respectively, p <0.001). Multivariate analysis demonstrated that eGFR ≤30, but not eGFR 31-60, was associated with increased risk of death (OR 3), bleeding (OR 5.2) and device implantation failure (HR 2.28). For each 10-mL/min decrease in eGFR, there was an associated relative increase in the risk of death (35%; p<0.001), cardiovascular death (14%; p=0.018), major bleeding 35% (p<0.001), and transcatheter valve failure (16%; p=0.007). Renal dysfunction was not associated with stroke or need for pacemaker implantation. In conclusion among patients undergoing TAVR, baseline renal dysfunction is an important independent predictor of morbidity and mortality.
Objectives This study was designed to assess the clinical course and to identify risk factors for life-threatening events in patients with long-QT syndrome (LQTS) with normal corrected QT (QTc) ...intervals. Background Current data regarding the outcome of patients with concealed LQTS are limited. Methods Clinical and genetic risk factors for aborted cardiac arrest (ACA) or sudden cardiac death (SCD) from birth through age 40 years were examined in 3,386 genotyped subjects from 7 multinational LQTS registries, categorized as LQTS with normal-range QTc (≤440 ms n = 469), LQTS with prolonged QTc interval (>440 ms n = 1,392), and unaffected family members (genotyped negative with ≤440 ms n = 1,525). Results The cumulative probability of ACA or SCD in patients with LQTS with normal-range QTc intervals (4%) was significantly lower than in those with prolonged QTc intervals (15%) (p < 0.001) but higher than in unaffected family members (0.4%) (p < 0.001). Risk factors ACA or SCD in patients with normal-range QTc intervals included mutation characteristics (transmembrane-missense vs. nontransmembrane or nonmissense mutations: hazard ratio: 6.32; p = 0.006) and the LQTS genotypes (LQTS type 1:LQTS type 2, hazard ratio: 9.88; p = 0.03; LQTS type 3:LQTS type 2, hazard ratio: 8.04; p = 0.07), whereas clinical factors, including sex and QTc duration, were associated with a significant increase in the risk for ACA or SCD only in patients with prolonged QTc intervals (female age >13 years, hazard ratio: 1.90; p = 0.002; QTc duration, 8% risk increase per 10-ms increment; p = 0.002). Conclusions Genotype-confirmed patients with concealed LQTS make up about 25% of the at-risk LQTS population. Genetic data, including information regarding mutation characteristics and the LQTS genotype, identify increased risk for ACA or SCD in this overall lower risk LQTS subgroup.
Liver steatosis may occur concomitantly in patients with chronic hepatitis B infection (CHB) and is implicated in increased morbidity and mortality. Hepatitis B virus (HBV) viral load is a marker for ...disease progression and long-term outcomes in CHB. We investigated the association between liver steatosis and HBV viral load and their individual effects on all-cause mortality and the development of cancer in patients with CHB and liver steatosis.
This retrospective study included 524 treatment-naïve patients with CHB, with a mean follow-up of 6 years. Liver biopsy was available for 170 patients and liver steatosis was validated by at least 3 ultrasonographic examinations.
A total of 241/524 (46%) patients with CHB had liver steatosis, with a strong correlation between the degree of liver steatosis as assessed by ultrasonography or by liver biopsy (r = 0.9, p <0.001). Although liver steatosis was not significantly associated with advanced fibrosis, a multivariate analysis showed that liver steatosis was associated with a 4-fold increased risk of all-cause mortality and cancer (hazard ratio 4.35; 95% CI 1.69–8.99; p <0.001), irrespective of other major metabolic factors. However, baseline HBV viral load was not significantly associated with this composite outcome (hazard ratio 1.65; p = 0.29). In addition, liver steatosis was inversely associated with HBV viral load.
Patients with CHB and liver steatosis have an increased risk of all-cause mortality and cancer development compared to patients with CHB without liver steatosis, regardless of their baseline HBV viral load. Although tending to have a lower baseline viral load, patients with CHB and liver steatosis should be closely monitored irrespective of viral load.
Patients with chronic hepatitis B infection (CHB) may have liver steatosis at the same time. Here we show that in patients with CHB, liver steatosis is significantly associated with all-cause mortality and cancer, irrespective of other major metabolic factors, and the effect of liver steatosis on mortality and cancer is stronger than the effect of hepatitis B viral load on these outcomes. Thus, patients with CHB and liver steatosis should be closely monitored, irrespective of their viral load.
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•HBV viral load is an important predictor of adverse outcomes in patients with chronic HBV (CHB).•Liver steatosis may co-occur with CHB but its effect on all-cause mortality and cancer has not been determined.•Liver steatosis is significantly associated with all-cause mortality and cancer in patients with CHB.•The effect of liver steatosis on mortality and cancer is stronger than the effect of HBV viral load.•Patients with CHB and liver steatosis should be closely monitored, irrespective of their viral load.
Graphical Abstract
Graphical Abstract
Factors influencing the observed risk of life-threatening cardiac events and advancement in medical management in subjects with a genetically confirmed inherited ...arrhythmia.
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