This study aimed to determine whether QRS morphology identifies patients who benefit from cardiac resynchronization therapy with a defibrillator (CRT-D) and whether it influences the risk of primary ...and secondary end points in patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT) trial.
Baseline 12-lead ECGs were evaluated with regard to QRS morphology. Heart failure event or death was the primary end point of the trial. Death, heart failure event, ventricular tachycardia, and ventricular fibrillation were secondary end points. Among 1817 patients with available sinus rhythm ECGs at baseline, there were 1281 (70%) with left bundle-branch block (LBBB), 228 (13%) with right bundle-branch block, and 308 (17%) with nonspecific intraventricular conduction disturbances. The latter 2 groups were defined as non-LBBB groups. Hazard ratios for the primary end point for comparisons of CRT-D patients versus patients who only received an implantable cardioverter defibrillator (ICD) were significantly (P < 0.001) lower in LBBB patients (0.47; P < 0.001) than in non-LBBB patients (1.24; P = 0.257). The risk of ventricular tachycardia, ventricular fibrillation, or death was decreased significantly in CRT-D patients with LBBB but not in non-LBBB patients. Echocardiographic parameters showed significantly (P < 0.001) greater reduction in left ventricular volumes and increase in ejection fraction with CRT-D in LBBB than in non-LBBB patients.
Heart failure patients with New York Heart Association class I or II and ejection fraction ≤ 30% and LBBB derive substantial clinical benefit from CRT-D: a reduction in heart failure progression and a reduction in the risk of ventricular tachyarrhythmias. No clinical benefit was observed in patients with a non-LBBB QRS pattern (right bundle-branch block or intraventricular conduction disturbances).
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.
Objectives The purpose of this study was to assess deformation dynamics and in vivo mechanical properties of the aortic annulus throughout the cardiac cycle. Background Understanding dynamic aspects ...of functional aortic valve anatomy is important for beating-heart transcatheter aortic valve implantation. Methods Thirty-five patients with aortic stenosis and 11 normal subjects underwent 256-slice computed tomography. The aortic annulus plane was reconstructed in 10% increments over the cardiac cycle. For each phase, minimum diameter, ellipticity index, cross-sectional area (CSA), and perimeter (Perim) were measured. In a subset of 10 patients, Young's elastic module was calculated from the stress-strain relationship of the annulus. Results In both subjects with normal and with calcified aortic valves, minimum diameter increased in systole (12.3 ± 7.3% and 9.8 ± 3.4%, respectively; p < 0.001), and ellipticity index decreased (12.7 ± 8.8% and 10.3 ± 2.7%, respectively; p < 0.001). The CSA increased by 11.2 ± 5.4% and 6.2 ± 4.8%, respectively (p < 0.001). Perim increase was negligible in patients with calcified valves (0.56 ± 0.85%; p < 0.001) and small even in normal subjects (2.2 ± 2.2%; p = 0.01). Accordingly, relative percentage differences between maximum and minimum values were significantly smallest for Perim compared with all other parameters. Young's modulus was calculated as 22.6 ± 9.2 MPa in patients and 13.8 ± 6.4 MPa in normal subjects. Conclusions The aortic annulus, generally elliptic, assumes a more round shape in systole, thus increasing CSA without substantial change in perimeter. Perimeter changes are negligible in patients with calcified valves, because tissue properties allow very little expansion. Aortic annulus perimeter appears therefore ideally suited for accurate sizing in transcatheter aortic valve implantation.
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 )
Objectives The aim of this study was to evaluate whether certain post-Maze left atrial (LA) contractile profiles may pose a risk for ischemic stroke. Background The 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. Methods Clinical, 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. Results At 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/m2 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. Conclusions Absence of LA contraction and LA volume index ≥33 ml/m2 result in a significant increase in the risk for thromboembolic stroke after the Maze procedure for patients in sinus rhythm.
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia characterized by syncope and sudden death occurring during exercise or acute emotion. CPVT is caused by ...abnormal intracellular Ca2+ handling resulting from mutations in the RyR2 or CASQ2 genes. Because CASQ2 and RyR2 are involved in different aspects of the excitation‐contraction coupling process, we hypothesized that these mutations are associated with different functional and intracellular Ca²+ abnormalities. To test the hypothesis we generated induced Pluripotent Stem Cell‐derived cardiomyocytes (iPSC‐CM) from CPVT1 and CPVT2 patients carrying the RyR2R420Q and CASQ2D307H mutations, respectively, and investigated in CPVT1 and CPVT2 iPSC‐CM (compared to control): (i) The ultrastructural features; (ii) the effects of isoproterenol, caffeine and ryanodine on the Ca2+i transient characteristics. Our major findings were: (i) Ultrastructurally, CASQ2 and RyR2 mutated cardiomyocytes were less developed than control cardiomyocytes. (ii) While in control iPSC‐CM isoproterenol caused positive inotropic and lusitropic effects, in the mutated cardiomyocytes isoproterenol was either ineffective, caused arrhythmias, or markedly increased diastolic Ca2+i. Importantly, positive inotropic and lusitropic effects were not induced in mutated cardiomyocytes. (iii) The effects of caffeine and ryanodine in mutated cardiomyocytes differed from control cardiomyocytes. Our results show that iPSC‐CM are useful for investigating the similarities/differences in the pathophysiological consequences of RyR2 versus CASQ2 mutations underlying CPVT1 and CPVT2 syndromes.
Catecholamine-induced polymorphic ventricular tachycardia (CPVT) is a familial disorder caused by cardiac ryanodine receptor type 2 (RyR2) or calsequestrin 2 (CASQ2) gene mutations. To define how ...CASQ2 mutations cause CPVT, we produced and studied mice carrying a human D307H missense mutation (CASQ(307/307)) or a CASQ2-null mutation (CASQ(DeltaE9/DeltaE9)). Both CASQ2 mutations caused identical consequences. Young mutant mice had structurally normal hearts but stress-induced ventricular arrhythmias; aging produced cardiac hypertrophy and reduced contractile function. Mutant myocytes had reduced CASQ2 and increased calreticulin and RyR2 (with normal phosphorylated proportions) but unchanged calstabin levels, as well as reduced total sarcoplasmic reticulum (SR) Ca(2+), prolonged Ca(2+) release, and delayed Ca(2+) reuptake. Stress further diminished Ca(2+) transients, elevated cytosolic Ca(2+), and triggered frequent, spontaneous SR Ca(2+) release. Treatment with Mg(2+), a RyR2 inhibitor, normalized myocyte Ca(2+) cycling and decreased CPVT in mutant mice, indicating RyR2 dysfunction was critical to mutant CASQ2 pathophysiology. We conclude that CPVT-causing CASQ2 missense mutations function as null alleles. In the absence of CASQ2, calreticulin, a fetal Ca(2+)-binding protein normally downregulated at birth, remains a prominent SR component. Adaptive changes to CASQ2 deficiency (increased posttranscriptional expression of calreticulin and RyR2) maintained electrical-mechanical coupling, but increased RyR2 leakiness, a paradoxical response further exacerbated by stress. The central role of RyR2 dysfunction in CASQ2 deficiency unifies the pathophysiologic mechanism underlying CPVT due to RyR2 or CASQ2 mutations and suggests a therapeutic approach for these inherited cardiac arrhythmias.
The aim of this study was to evaluate the significance of increased left atrial (LA) volume determined within the first 48 h of admission as a long-term predictor of outcome in patients with acute ...myocardial infarction (MI).
The LA volume reflects left ventricular (LV) diastolic properties. Whereas other LV Doppler diastolic characteristics are influenced by acute changes in LV function, LA volume is stable and reflects diastolic properties before MI.
Clinical and echocardiographic parameters were prospectively collected in 395 consecutive patients with acute MI. Patients with LA volume index (LAVI) >32 ml/m2(normal + 2 standard deviations) were compared with those with LAVI ≤32 ml/m2. Independent clinical and echocardiographic prognostic risk factors for five years' mortality were determined by the Cox proportional hazard model.
Left atrial volume index >32 ml/m2was found in 63 patients (19%) who had a higher incidence of congestive heart failure on admission (24% vs. 12%, p < 0.01), a higher incidence of mitral regurgitation, increased LV dimensions, and reduced LV ejection fraction when compared with patients with LAVI ≤32 ml/m2. Their five-year mortality rate was 34.5% versus 14.2% (p < 0.001). Significant independent risk predictors of five years' mortality were age (10 years) (odds ratio OR 1.45; 95% confidence interval CI1.14 to 1.86), Killip class ≥2 on admission (OR 2.30; 95% CI 1.29 to 4.09), LAVI >32 ml/m2(OR 2.22; 95% CI 1.25 to 3.96), diabetes (OR 1.94; 95% CI 1.15 to 3.28), and LV restrictive filling pattern (OR 1.89; 95% CI 1.09 to 3.31).
In patients with acute MI, increased LA volume, determined within the first 48 h of admission, is an independent predictor of five-year mortality with incremental prognostic information to clinical and echocardiographic data.
Triggers and Timing of Acute Coronary Syndromes Tofler, Geoffrey H., MD; Kopel, Eran, MD; Klempfner, Robert, MD ...
The American journal of cardiology,
05/2017, Letnik:
119, Številka:
10
Journal Article
Recenzirano
Abstract Prior studies have shown that an acute coronary syndrome (ACS) may be triggered by external activities, however their frequency, predictors and significance are uncertain. We evaluated data ...from The National Israel Survey of Acute Coronary Syndromes, which was conducted in 2004 (February-March) in all 25 coronary care units and cardiac wards in Israel. Demographic and clinical data were recorded for consecutive participants, including potential triggers and time of symptom onset of ACS. Among the 1849 patients who completed the trigger question, one quarter (25.9%) reported a possible trigger, comprising heavy physical exertion (15.2%), emotional stress (8.3%), anger (1.1%), heavy meal (1.3%) and sexual activity (0.5%). Predictors of a triggered ACS were age <65 years, prior angina, no prior ACE / AT2 inhibitors, impaired functional class, not having typical chest pain on admission, and a final diagnosis of unstable angina. The highest proportion of triggered ACS was between noon- 6pm. Physical exertion as a trigger was associated with reduced in-hospital mortality (0.4 versus 2.8%, p <0.05) and 1-year mortality. Emotional stress as a trigger did not influence in-hospital or 1-year mortality, however among those discharged from hospital, it was associated with increased 30-day rehospitalisation (27.6 versus 19.3%, p <0.05) and a trend towards increased mortality (4.1 versus 2.0%, p=0.10).
There is controversy regarding type of bundle branch block (BBB) that is associated with increased mortality risk in patients with heart failure (HF). The present study was designed to explore the ...association between BBB pattern and long-term mortality in hospitalized patients with systolic HF. Risk of 4-year all-cause mortality was assessed in 1,888 hospitalized patients with systolic HF (left ventricular ejection function <50%) without a pacemaker in a prospective national survey. Cox proportional hazards regression modeling was used to compare mortality risk in patients with right BBB (RBBB; 10%), left BBB (LBBB; 14%), and no BBB (76%) on admission electrocardiogram. At 4 years of follow up, mortality rates were highest in patients with RBBB (69%), intermediate in those with LBBB (63%), and lowest in those without BBB (50%, p <0.001). Multivariate analysis demonstrated a significant 36% increased mortality risk in patients with RBBB versus no BBB (p = 0.002) but no significant difference in mortality risk for patients with LBBB versus no BBB (hazard ratio 1.04, p = 0.66). RBBB versus LBBB was associated with a 29% (p = 0.035) increased risk for 4-year mortality in the total population and with a 58% (p = 0.015) increased risk in patients with ejection fraction <30%. In conclusion, RBBB but not LBBB on admission electrocardiogram is associated with a significant increased long-term mortality risk in hospitalized patients with systolic HF. Deleterious effects of RBBB compared to LBBB appear to be more pronounced in patients with more advanced left ventricular dysfunction.
Novel HCN4 Mutation. Objectives: To conduct a clinical, genetic, and functional analysis of 3 unrelated families with familial sinus bradycardia (FSB).
Background:
Mutations in the ...hyperpolarization‐activated nucleotide‐gated channel (HCN4) are known to be associated with FSB.
Methods and Results:
Three males of Moroccan Jewish descent were hospitalized: 1 survived an out‐of‐hospital cardiac arrest and 2 presented with weakness and presyncopal events. All 3 had significant sinus bradycardia, also found in other first‐degree relatives, with a segregation suggesting autosomal‐dominant inheritance. All had normal response to exercise and normal heart structure. Sequencing of the HCN4 gene in all patients revealed a C to T transition at nucleotide position 1,454, which resulted in an alanine to valine change (A485V) in the ion channel pore found in most of their bradycardiac relatives, but not in 150 controls. Functional expression of the mutated ion channel in Xenopus oocytes and in human embryonic kidney 293 cells revealed profoundly reduced function and synthesis of the mutant channel compared to wild‐type.
Conclusions:
We describe a new mutation in the HCN4 gene causing symptomatic FSB in 3 unrelated individuals of similar ethnic background that may indicate unexplained FSB in this ethnic group. This profound functional defect is consistent with the symptomatic phenotype. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1365‐1372, December 2010)
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