Reduced inferior wall longitudinal strain is associated with malignant arrhythmias in non-ischemic heart failure.

BACKGROUND: Reduced systolic myocardial function in the inferior region of the left ventricle has been suggested to be associated with malignant arrhythmias. We tested this hypothesis in patients with non-ischemic heart failure. METHODS: Patients with non-ischemic heart failure (left ventricular ejection fraction [LVEF] < 35%) were evaluated by 2D-speckle-tracking echocardiography. The regional longitudinal strain was calculated for each of the six left ventricular walls. The reduced regional function was defined as strain below the median. The outcome was a composite of sudden cardiac death, admission with sustained ventricular arrhythmia, resuscitated cardiac arrest, and appropriate therapy from a primary prophylactic implantable cardioverter defibrillator. Time-to-first-event analysis was performed using a Cox model. RESULTS: From two centers, 401 patients were included (median age: 63 years, 72% male) with a median LVEF of 25% (interquartile range [IQR] 20;30), and a median inferior wall strain of -9.0% (-12.5; -5.4). During a median follow-up of 4.0 years, 52 outcomes occurred. After multivariate adjustment for clinical and electrocardiographic parameters, inferior wall strain was independently associated with the outcome (HR 2.50 [1.35; 4.62], p = .003). No independent association was found between the composite outcome and reduced strain in any of the other left ventricular walls, Global Longitudinal Strain (HR 1.66 [0.93; 2.98], p = .09), or LVEF (HR 1.33 [0.75; 2.33], p = .33). CONCLUSIONS: Below median strain in the left ventricular inferior region was independently associated with a 2.5-fold increase in the risk of malignant arrhythmias and sudden cardiac death in patients with non-ischemic heart failure.

Temporal changes in the surgical management of patients with tetralogy of Fallot in Denmark: a nationwide cohort study.

OBJECTIVES: To assess temporal changes in the surgical management of patients with tetralogy of Fallot including the timing of interventions, surgical techniques, reinterventions and survival in a nationwide cohort. METHODS: Patients with tetralogy of Fallot in Denmark were divided into 3 eras based on their year of birth: early (1977-1991), intermediate (1992-2006) and late (2007-2021). RESULTS: The cohort consisted of 745 patients. Median follow-up was 21.2 years (13.7-30.5). There was a temporal trend towards less shunt palliation (-0.3% per year, 95% CI -0.05 to -0.1). Median age at intracardiac repair was 2.9 years (1.8-5.0), 0.8 years (0.5-1.3) and 0.5 years (0.4-0.7) (P < 0.001) in the early, intermediate and late era, respectively. There was a temporal trend towards less valve-sparing repair (-0.7% per year, 95% CI -0.5 to -1.0) and more repair with transannular patches (0.7% per year, 95% CI 0.5-1.0). Survival at 10 years was 79% (64-76), 90% (87-93) and 95% (92-98) (P < 0.001) and pulmonary valve replacement within the first 10 years after intracardiac repair was performed in 3% (1-6), 12% (8-16) and 21% (13-29) (P < 0.001) in the early, intermediate and late era, respectively. CONCLUSIONS: There was a temporal trend towards less shunt palliation and intracardiac repair at a younger age with more use of transannular patches. While survival throughout childhood and adolescence has improved, more patients undergo pulmonary valve replacement during the first 10 years after intracardiac repair.

Use of torsades de pointes risk drugs among patients with out-of-hospital cardiac arrest and likelihood of shockable rhythm and return of spontaneous circulation: A nationwide study.

AIM: Treatment with certain drugs can augment the risk of developing malignant arrhythmias (e.g. torsades de pointes [TdP]). Hence, we examined the overall TdP risk drug use before out-of-hospital cardiac arrest (OHCA) and possible association with shockable rhythm and return of spontaneous circulation (ROSC). METHODS: Patients ≥18 years with an OHCA of cardiac origin from the Danish Cardiac Arrest Registry (2001-2014) and TdP risk drug use according to www.CredibleMeds.org were identified. Factors associated with TdP risk drug use and secondly how use may affect shockable rhythm and ROSC were determined by multivariable logistic regression. RESULTS: We identified 27,481 patients with an OHCA of cardiac origin (median age: 72 years [interquartile range 62.0, 80.0 years]). A total of 37% were in treatment with TdP risk drugs 0-30 days before OHCA compared with 33% 61-90 days before OHCA (p < 0.001). Most commonly used TdP risk drugs were citalopram (36.1%) and roxithromycin (10.7%). Patients in TdP risk drug treatment were older (75 vs 70 years) and more comorbid compared with those not in treatment. Subsequently, TdP risk drug use was associated with less likelihood of the presenting rhythm being shockable (odds ratio [OR] = 0.63, 95% confidence interval [CI]:0.58-0.69) and ROSC (OR = 0.73, 95% CI:0.66-0.80). CONCLUSION: TdP risk drug use increased in the time leading up to OHCA and was associated with reduced likelihood of presenting with a shockable rhythm and ROSC in an all-comer OHCA setting. However, patients in TdP risk drug treatment were older and more comorbid than patients not in treatment.

Targeted potassium levels to decrease arrhythmia burden in high risk patients with cardiovascular diseases (POTCAST): Study protocol for a randomized controlled trial.

BACKGROUND: Low plasma potassium (p-K) is associated with increased risk of malignant arrhythmia and observational studies indicate protective effects of p-K in the upper reference level. However, randomized clinical studies are needed to document whether actively increasing p-K to high-normal levels is possible and safe and improves cardiovascular outcomes. OBJECTIVE: To investigate if increased p-K reduces the risk of malignant arrhythmia and all-cause death in high-risk patients with a cardiovascular disease treated with an implantable cardioverter defibrillator (ICD) for primary or secondary preventive causes. Secondly, to investigate whether high-normal p-K levels can be safely reached and maintained using already available medications and potassium-rich dietary guidance. METHODS: This is a prospective, randomized, and open-labelled study enrolling patient at high-risk of malignant arrhythmias. According to sample size calculations, 1,000 patients will be randomized 1:1 to either an investigational regiment that aims to increase and maintain p-K at high-normal levels (4.5-5.0 mmol/L) or to usual standard of care and followed for an expected four years. The trial will run until a total of 291 events have occurred providing an α = 0.05 and 1-ß = 0.80. The composite primary endpoint includes ventricular tachycardia >125 bpm lasting >30 seconds, any appropriate ICD-therapy, and all-cause mortality. At present, 739 patients have been randomized. CONCLUSIONS: We present the rationale for the design of the POTCAST trial. The inclusion was initiated 2019 and is expected to be finished 2022. The study will show if easily available treatments to increase p-K may be a new treatment modality to protect against malignant arrythmias.

Comparison of the Anterior Septal Line and Mitral Isthmus Line for Perimitral Atrial Flutter Ablation Using Robotic Magnetic Navigation.

BACKGROUND: Perimitral atrial flutter (PMAFL) is one of the most common macro-reentrant left atrial tachycardias. Mitral isthmus (MI) linear ablation is a common strategy for the treatment of PMAFLs, and anterior septum (AS) linear ablation has emerged as a novel ablation approach. We aimed at assessing the effectiveness of AS linear ablation using robotic magnetic navigation for PMAFL ablation. METHODS: In this retrospective study, a total of 36 consecutive patients presented with AFL as the unique arrhythmia or accompanied with atrial fibrillation (AF) who underwent catheter ablation were enrolled. Patients were classified into two groups according to the different ablation strategies, the MI line group (10 patients) and the AS line group (26 patients). RESULTS: The clinical baseline characteristics of patients in the two groups were nearly identical. There were no significant differences in procedure time (148.7 ± 46.1 vs. 123.2 ± 30.1 min, P=0.058) or radiofrequency ablation time (25.9 ± 11.4 vs. 23.5 ± 12.6 min) between the two groups. Fluoroscopy time was longer in the MI line group (8.0 ± 4.4 vs. 5.1 ± 2.7 min, P=0.024), and the acute success rate was higher in the AS line group versus the MI line group (96.2% vs. 70%, P=0.025). The long-term freedom from arrhythmia survival rate was higher in the AS line group (73%) than in the MI line group (40%) after a mean follow-up time of 37.4 months with a 3-month blanking period (P=0.049). CONCLUSIONS: AS linear ablation is an effective and safe strategy for PMAFL ablation using robotic magnetic navigation.

Clinical outcome in patients with implantable cardioverter-defibrillator and cancer: a nationwide study.

AIMS: Patients with cancer are insufficiently represented in randomized clinical trials investigating efficacy of implantable cardioverter-defibrillators (ICDs). We aimed to describe outcomes in patients with a pre-existing diagnosis of cancer at time of ICD implantation. METHODS AND RESULTS: We utilized Danish nationwide registries to identify primary and secondary prevention ICD implantations from 2007 to 2012. Multivariable Cox models were used to assess the risk of appropriate ICD therapy and mortality in patients with and without cancer at time of implantation. During a median follow-up of 2.1 years, 2935 primary prevention ICD and 2730 secondary prevention ICD implantations were identified. Out of these [289 (5.1%)] had pre-existing cancer [primary 140 (4.8%), secondary 149 (5.5%)]. No differential risk for appropriate ICD therapy was found between patients with or without cancer, [primary cancer: 19/140, no cancer: 380/2795, hazard ratio (HR) = 1.07 (0.67-1.69)] and [secondary cancer: 42/149, no cancer: 699/2581, HR = 1.28 (0.93-1.75)]. In primary patients, cancer was not associated with higher risk of 1-year [cancer: 10/140, no cancer: 133/2795, HR = 1.20 (0.84-2.28)] or all-time mortality [cancer: 22/140, no cancer: 339/2795, HR = 1.13 (0.74-1.75)]. In secondary patients, cancer was associated with a higher 1-year [cancer: 19/149, no cancer: 108/2581, HR = 2.62 (1.60-4.29)] and all-time mortality [cancer: 44/149, no cancer: 315/2581, HR = 2.36 (1.71-3.24)]. CONCLUSION: Implantable cardioverter-defibrillators were implanted in a minority of cancer patients. No difference in risk of appropriate therapy was observed between cancer and non-cancer patients, regardless of implant indication. Cancer was associated with increased mortality in secondary prevention ICD patients, but not in primary prevention ICD patients. In secondary prevention ICD patients, the majority of deaths were attributable to cancer.

The impact of co-morbidity burden on appropriate implantable cardioverter defibrillator therapy and all-cause mortality: insight from Danish nationwide clinical registers.

AIMS: In a nationwide cohort of primary (PP-ICD) and secondary prevention (SP-ICD) implantable cardioverter defibrillator (ICD) patients, we aimed to investigate the association between co-morbidity burden and risk of appropriate ICD therapy and mortality. METHODS AND RESULTS: We identified all patients >18 years, implanted with first-time PP-ICD (n = 1873) or SP-ICD (n = 2461) in Denmark from 2007 to 2012. Co-morbidity was identified in administrative registers of hospitalization and drug prescription from pharmacies. Co-morbidity burden was defined as the number of pre-existing non-ICD indication-related co-morbidities including atrial fibrillation, diabetes, chronic obstructive pulmonary disease, chronic renal disease, liver disease, cancer, chronic psychiatric disease, and peripheral and/or cerebrovascular disease, and divided into four groups (co-morbidity burden 0, 1, 2, and ≥3). Through Cox models, we assessed the impact of co-morbidity burden on appropriate ICD therapy and mortality. Increasing co-morbidity burden was not associated with increased risk of appropriate therapy, irrespective of implant indication [all hazard ratios (HRs) 1.0-1.4, P = NS]. Using no co-morbidities as reference, increasing co-morbidity burden was associated with increased mortality risk in PP-ICD patients (co-morbidity burden 1, HR 2.1; comorbidity burden 2, HR 3.7; co-morbidity burden ≥3, HR 6.6) (all P < 0.001) and SP-ICD patients (co-morbidity burden 1, HR 2.2; co-morbidity burden 2, HR 3.8; co-morbidity burden ≥3, HR 5.8). With increasing co-morbidity burden, an increasing frequency of patients died without having utilized their device, with 72% PP-ICD and 45% SP-ICD patients with co-morbidity burden ≥3 dying without prior appropriate ICD therapy. CONCLUSION: Increasing co-morbidity burden was not associated with increased risk of appropriate ICD therapy. With increasing co-morbidity burden, mortality increased, and a higher proportion of patients died, without ever having utilized their device.

Is modification of the VVI backup mode in implantable cardioverter-defibrillators from St Jude medical required due to increased risk of inappropriate shocks?

Inappropriate implantable cardioverter-defibrillator (ICD) shock therapy is painful, stressful, and typically occurs unexpected in conscious patients and may be related to a less favourable prognosis. In our institution, we have observed four cases of multiple inappropriate ICD shocks during reset to VVI backup mode. All four patients were implanted with a St Jude Medical ICD since 2010. The reset to VVI backup mode happens as a 'safety' response when the ICD encounters errors in the software or hardware often due to electromagnetic interference. The ICD then operates in a simple mode, with only a ventricular fibrillation (VF) zone starting at 146 b.p.m., with shock therapy only and changes in sensitivity settings making the ICD more sensitive. In all cases, the reason for the multiple inappropriate shocks was that the VF zone was reached due to exercise-induced sinus tachycardia or due to oversensing during sinus rhythm. The VVI backup mode has to balance between protection from failure of ICD therapy during life-threatening ventricular arrhythmias and from inappropriate shocks. It seems the non-programmable parameters in VVI backup mode of St Jude Medical ICDs carry an unacceptable high risk of inappropriate shocks during normal rhythm as illustrated by our four cases. A higher VF zone comparable with the zones chosen by the other manufacturer would give a better balance, since it is very unlikely that a patient will need shock therapy urgently for slow ventricular tachycardia.

Stromal cell-derived factor 1α (SDF-1α): A marker of disease burden in patients with atrial fibrillation.

OBJECTIVES: Stromal cell-derived factor 1a (SDF-1α), is a chemokine and is able to home hematopoietic progenitor cells to injured areas of heart tissue for structural repair. Previous studies have found increased levels of SDF-1α in several cardiac diseases, but only few studies have investigated SDF-1α in patients with atrial fibrillation (AF). We aimed to test SDF-1α in a large cohort of patients with AF and its role as a prognostic marker. DESIGN: Between January 1st 2008 to December 1st 2012, 290 patients with ECG documented AF were enrolled from the in- and outpatient clinics at the Department of Cardiology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark. Plasma levels of SDF-1α were measured using ELISA technique. Clinical data were registered and patient follow-up was conducted. RESULTS: Patients with permanent AF had significantly higher SDF-1α levels (2199.5 pg/ml) than the patients with paroxysmal AF (1982.0 pg/ml) and persistent AF (1906.0 pg/ml), p < 0.0005. Higher SDF-1α level was associated with longer time spent in the hospital per readmission, p < 0.05. CONCLUSION: In AF patients, a higher SDF-1α level was found in patients with a more progressive state of arrhythmia and was associated with longer hospitalizations. These findings suggest that SDF-1α could prove valuable in risk stratification and evaluating the disease burden in AF patients.

Heart rate variability density analysis (Dyx) for identification of appropriate implantable cardioverter defibrillator recipients among elderly patients with acute myocardial infarction and left ventricular systolic dysfunction.

AIMS: Dyx is a new heart rate variability (HRV) density analysis specifically designed to identify patients at high risk for malignant ventricular arrhythmias. The aim of this study was to test if Dyx can improve risk stratification for malignant ventricular tachyarrhythmias and to test if the previously identified cut-off can be reproduced. METHODS AND RESULTS: This study included 248 patients from the CARISMA study with ejection fraction ≤40% after an acute myocardial infarction and an analysable 24 h Holter recording. All patients received an implantable cardiac monitor, which was used to diagnose the primary endpoint of near-fatal or fatal ventricular tachyarrhythmias likely preventable by an implantable cardioverter defibrillator (ICD), during a period of 2 years. A Dyx ≤ 1.96 was considered abnormal. The secondary endpoint was cardiovascular death. At enrolment 59 patients (24%) had a Dyx ≤ 1.96 and 20 experienced a primary endpoint. A Dyx ≤ 1.96 was associated with a significantly increased risk for malignant arrhythmias [hazards ratio (HR) = 4.36 (1.81-10.52), P = 0.001] and cardiovascular death [HR = 3.47 (1.38-8.74), P = 0.008]. Compared with important clinical risk parameters (age >70 years and QRS > 120 ms), Dyx ≤ 1.96 significantly added predictive value (P = 0.0066). CONCLUSIONS: Dyx was a better predictor of ventricular tachyarrhythmias than the traditional measures of HRV and heart rate turbulence, particularly in the elderly. Dyx might be a useful tool for better selection of ICD candidates in the elderly population, since a normal Dyx in this group was associated with a very low risk for malignant ventricular arrhythmias.ClinicalTrials.gov Identifier NCT00145119.

New-onset atrial fibrillation predicts malignant arrhythmias in post-myocardial infarction patients--a Cardiac Arrhythmias and RIsk Stratification after acute Myocardial infarction (CARISMA) substudy.

BACKGROUND: After myocardial infarction (MI) the risk of sudden cardiac death due to arrhythmias is substantial. OBJECTIVE: The purpose of this study was to investigate if new-onset atrial fibrillation (AF) is associated with development of potential malignant brady- and tachyarrhythmias after an acute MI. METHODS: The study included 277 post-MI patients from the CARISMA study with left ventricular ejection fraction ≤ 40%, New York Heart Association class I, II, or III and no history of AF. All patients were implanted with an implantable cardiac monitor within 4 to 27 days after an acute MI and followed every 3 months for 2 years. Time-dependent association between new-onset AF > 30 s and the development of bradyarrhythmias and/or ventricular tachyarrhythmias were investigated using Cox proportional hazard regressions. RESULTS: New-onset AF was associated with an increased risk of bradyarrhythmias when adjusting for male gender and baseline age, left ventricular ejection fraction and QRS width (HR = 2.8 [1.3-5.8], P = .006). Similarly, new-onset AF predicted ventricular tachyarrhythmias when adjusting for New York Heart Association class ≥ II and baseline QRS width (HR = 2.3 [1.2-4.4], P = .019). After dividing ventricular tachyarrhythmias into subgroups of non-sustained ventricular tachycardia (VT), sustained VT and ventricular fibrillation (VF), new-onset AF was significantly associated with an increased risk of non-sustained- and sustained VT but not VF (non-sustained VT: HR = 3.5 [1.7-7.2], P < .001, sustained VT: HR = 4.2 [1.1-15.7], P = .035, VF: HR = 1.1 [0.2-5.8], P = .877). CONCLUSION: In patients surviving a MI with reduced left ventricular systolic function, new-onset AF is associated with a significantly increased risk of developing ventricular brady- and tachyarrhythmias.

Bloqueo aurículoventricular de alto grado que complica el infarto de miocardio con elevación ST en la era de la intervención coronaria percutánea primaria

Resumen Finalidades: la intervención percutánea coronaria primaria (pPCI, por sus siglas en inglés) ha reemplazado la trombolisis como tratamiento de elección para el infarto de miocardo con elevación del segmento ST (STEMI por sus siglas en inglés). Sin embargo, la incidencia y la importancia pronóstica del bloqueo aurículoventricular de alto grado (BAV-AG) en pacientes con STEMI en la era de pPCI han sido poco estudiadas. El objetivo de este estudio fue evaluar la incidencia, los predictores y la importancia pronóstica of BAV-AG en pacientes con STEMI tratados con pPCI. Métodos y resultados: este estudio incluyó 2073 pacientes con STEMI tratado con pPCI. Los pacientes fueron identificados a través de un registro hospitalario y el Registro Nacional de Pacientes de Dinamarca. Ambos registros se usaron también para establecer el diagnóstico de BAV-AG. La mortalidad por todas las causas fue la variable evaluable primaria. Durante un seguimiento con una mediana de 2,9 años [rango del intercuartil (IQR): 1,8-4,0] fallecieron 266 pacientes. Se documentó bloqueo aurículoventricular de alto grado en 67 (3,2%) pacientes, 25 de los cuales murieron. Entre los predictores independientes importantes de presentar BAV-AG, se incluyeron la oclusión de la arteria coronaria derecha, edad >65 años, género femenino, hipertensión, y diabetes. La tasa de mortalidad ajustada aumentó significativamente en pacientes con BAV-AG comparado con pacientes sin BAV-AG [cociente de riesgos instantáneos » 3,14 (intervalo de confianza 95%: 2,04-4,84), P < 0,001]. Un análisis relevante 30 días después del STEMI mostró iguales tasas de mortalidad en los dos grupos. Conclusión: la incidencia de BAV-AG en pacientes con STEMI tratado con pPCI se ha reducido comparado con los informes de la era trombolítica. Sin embargo, a pesar de esta mejora, en la era de pPCI el bloqueo AV de alto grado sigue siendo un marcador pronóstico severo. La tasa de mortalidad solo aumentó dentro de los primeros 30 días. Los pacientes con bloqueo aurículoventricular de alto grado que sobrevivieron más allá de este punto temporal tuvieron así un pronóstico igual al de los pacientes sin BAV-AG

Summary Aims: Primary percutaneous coronary intervention (pPCI) has replaced thrombolysis as treatment-of-choice for ST-segment elevation myocardial infarction (STEMI). However, the incidence and prognostic significance of high-degree atrioventricular block (HAVB) in STEMI patients in the pPCI era has been only sparsely investigated. The objective of this study was to assess the incidence, predictors and prognostic significance of HAVB in STEMI patients treated with pPCI. Methods and results: This study included 2073 STEMI patients treated with pPCI. The patients were identified through a hospital register and the Danish National Patient Register. Both registers were also used to establish the diagnosis of HAVB. All-cause mortality was the primary endpoint. During a median follow-up of 2.9 years [interquartile range (IQR) 1.8-4.0] 266 patients died. High-degree atrioventricular block was documented in 67 (3.2%) patients of whom 25 died. Significant independent predictors of HAVB included right coronary artery occlusion, age .65 years, female gender, hypertension, and diabetes. The adjusted mortality rate was significantly increased in patients with HAVB compared to patients without HAVB [hazard ratio = 3.14 (95% confidence interval 2.04-4.84), P < 0.001]. A landmark-analysis 30 days post-STEMI showed equal mortality rates in the two groups. Conclusion: The incidence of HAVB in STEMI patients treated with pPCI has been reduced compared with reports from the thrombolytic era. However, despite this improvement high-degree AV block remains a severe prognostic marker in the pPCI era. The mortality rate was only increased within the first 30 days. High-degree atrioventricular block patients who survived beyond this time-point thus had a prognosis equal to patients without HAVB

Influence of diabetes mellitus on inappropriate and appropriate implantable cardioverter-defibrillator therapy and mortality in the Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT) Trial.

BACKGROUND: The relationship between diabetes mellitus and risk of inappropriate or appropriate therapy in patients receiving an implantable cardioverter-defibrillator (ICD) and resynchronization therapy has not been investigated thoroughly. The effect of innovative ICD programming on therapy delivery in these patients is unknown. METHODS AND RESULTS: The Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT) randomized patients with a primary prophylactic ICD indication to 3 different types of ICD programming: conventional programming with a ventricular tachycardia zone of 170 to 199 bpm (arm A), high-rate cutoff with a ventricular tachycardia zone ≥200 bpm (arm B), or 60-second-delayed therapy (arm C). The end points of inappropriate therapy, appropriate therapy, and death were assessed among 485 patients with and 998 without diabetes mellitus. Innovative ICD programming reduced the risk of inappropriate therapy regardless of diabetes mellitus, although a trend toward a more pronounced effect of high-rate cutoff programming was seen in patients without diabetes mellitus (P for interaction=0.06). Diabetes mellitus was associated with a decreased risk of inappropriate therapy (hazard ratio, 0.54; 95% confidence interval, 0.36-0.80; P=0.002) and increased risk of appropriate therapy (hazard ratio, 1.58; 95% confidence interval, 1.17-2.14; P=0.003). In diabetic patients, there was significantly increased risk of death in those who had inappropriate therapy (hazard ratio, 4.17; 95% confidence interval, 1.52-11.40; P=0.005) and appropriate therapy (hazard ratio, 2.49; 95% confidence interval, 1.06-5.87; P=0.037) compared with those who did not. CONCLUSIONS: Innovative high-rate cutoff or delayed ICD programming was associated with a reduction in inappropriate therapy in patients with and without diabetes mellitus. Diabetes mellitus was associated with lower risk of inappropriate therapy but higher risk of appropriate therapy. Appropriate and inappropriate ICD therapy was associated with increased mortality in diabetic patients. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT00947310.

Myocardial performance is reduced immediately prior to ventricular ectopy.

BACKGROUND: We recently demonstrated local voltage potentials indicating conduction impairment and block in the sinus beats preceding ventricular premature beats (VPBs) originating in the ventricular outflow tracts. OBJECTIVE: The purpose of this study was to test the hypothesis that impairment of impulse conduction would also lead to changes in the contractile performance of sinus beats preceding ventricular ectopy using Tissue Doppler echocardiography. METHODS: Twenty-three consecutive patients with VPBs were examined in the apical 4-chamber view with a frame rate of 150 Hz (GE VIVID VII). Eleven patients had no structural heart disease, 5 had dilated cardiomyopathy, 4 had ischemic heart disease, 2 had arrhythmogenic right ventricular dysplasia, and 1 had aortic stenosis. The ectopy originated in the ventricular outflow tracts in 15 patients and in the left ventricle 8. Eleven of the patients underwent radiofrequency ablation of the VPBs. RESULTS: Tissue Doppler imaging demonstrated a highly statistically significant decrease in myocardial performance in the last sinus beat before the VPB compared to earlier sinus beats. Thus, ejection time (time to peak end-systolic contraction) and peak systolic velocity shortened significantly (P <.001 for both) with a subsequent reduction in systolic shortening (end-systolic displacement; P <.001). CONCLUSION: Ventricular ectopy is preceded by a significant decrease in myocardial performance in the last sinus beat preceding VPBs as observed in consecutive patients with a broad variety of heart conditions pointing to a mutual underlying electrical mechanism (ie, localized conduction block confined to an area surrounding the ectopic pacemaker).

Speckle-tracking echocardiography for predicting outcome in chronic aortic regurgitation during conservative management and after surgery.

OBJECTIVES: The aim of this study was to test myocardial deformation imaging using speckle-tracking echocardiography for predicting outcomes in chronic aortic regurgitation. BACKGROUND: In chronic aortic regurgitation, left ventricular (LV) dysfunction must be detected early to allow timely surgery. Speckle-tracking echocardiography has been proposed for this purpose, but the clinical value of this method in aortic regurgitation has not been established. METHODS: A longitudinal study was performed in 64 patients with moderate to severe aortic regurgitation. Thirty-five patients were managed conservatively with frequent clinical visits and sequential echocardiography and followed for an average of 19 ± 8 months, while 29 patients underwent surgery for the valve lesion and were followed for 6 months post-operatively. Baseline LV function by speckle-tracking and conventional echocardiography was compared with impaired outcome after surgery (defined as persisting symptoms or persisting LV dilation [LV end-diastolic volume index ≥ 87 ml/m(2)] or dysfunction [LV ejection fraction <50%]) and with disease progression during conservative management (defined as development of symptoms, increase in LV volume >15%, or decrease in LV ejection fraction >10%). RESULTS: Reduced myocardial systolic strain, systolic strain rate, and early diastolic strain rate by speckle-tracking echocardiography was associated with disease progression during conservative management (-16.3% vs. -19.0%, p = 0.02; -1.04 vs. -1.19 s(-1), p = 0.02; and 1.20 vs. 1.60 s(-1), p = 0.002, respectively) and with impaired outcome after surgery (-11.5% vs. -15.6%, p = 0.01; -0.88 vs. -1.01 s(-1), p = 0.04; and 0.98 vs. 1.33 s(-1), p = 0.01, respectively). Conventional parameters of LV function and size (LV ejection fraction and LV end-diastolic volume index) were associated with outcome after surgery (p = 0.04 and p = 0.01, respectively) but not with outcome during conservative management (p = 0.57 and p = 0.39, respectively). CONCLUSIONS: Speckle-tracking echocardiography is useful for the early detection of LV systolic and diastolic dysfunction in chronic aortic regurgitation.

Long QT syndrome in patients over 40 years of age: increased risk for LQTS-related cardiac events in patients with coronary disease.

BACKGROUND: Previous studies of long QT syndrome (LQTS) have focused primarily on the clinical course of affected patients up to 40 years of age to avoid the confounding influence of acquired heart disease on LQTS-related cardiac events in this genetic disorder. METHODS: Patients were identified as having coronary disease if they had a history of hospitalization for myocardial infarction, coronary angioplasty, coronary artery bypass graft surgery, or were treated with medication for angina. LQTS-related cardiac events included the first occurrence of syncope, aborted cardiac arrest, or sudden cardiac death without evidence suggestive of an acute coronary event. Cox proportional hazards regression modeling was used to analyze the independent contribution of coronary disease to LQTS-related cardiac events. RESULTS: Time-dependent coronary disease was associated with an increased risk of LQTS-related cardiac events (hazard ratio 2.24, 95% confidence interval 1.23-4.07, P = 0.008) after adjustment for syncopal history before age 40, QTc, and gender. Factors such as diabetes and hypertension that increase the risk for coronary disease were not associated with an increased risk for LQTS-related cardiac events. CONCLUSIONS: This is the first study to demonstrate that coronary disease augments the risk for LQTS-related cardiac events in LQTS. The findings highlight the need for more focused preventive therapy in LQTS patients above the age of 40.

Effect of dexamethasone on skeletal muscle Na+,K+ pump subunit specific expression and K+ homeostasis during exercise in humans.

The effect of dexamethasone on Na(+),K(+) pump subunit expression and muscle exchange of K(+) during exercise in humans was investigated. Nine healthy male subjects completed a randomized double blind placebo controlled protocol, with ingestion of dexamethasone (Dex: 2 x 2 mg per day) or placebo (Pla) for 5 days. Na(+),K(+) pump catalytic alpha1 and alpha2 subunit expression was approximately 17% higher (P < 0.05) and the structural beta1 and beta2 subunit expression was approximately 6-8% higher (P < 0.05) after Dex compared with Pla. During one-legged knee-extension for 10 min at low intensity (LI; 18.6 +/- 1.0 W), two moderate intensity (51.7 +/- 2.4 W) exercise bouts (MI(1): 5 min; 2 min recovery; MI(2): exhaustive) and two high-intensity (71.7 +/- 2.5 W) exercise bouts (HI(1): 1 min 40 s; 2 min recovery; HI(2): exhaustive), femoral venous K(+) was lower (P < 0.05) in Dex compared with Pla. Thigh K(+) release was lower (P < 0.05) in Dex compared with Pla in LI and MI, but not in HI. Time to exhaustion in MI(2) tended to improve (393 +/- 50 s versus 294 +/- 41 s; P = 0.07) in Dex compared with Pla, whereas no difference was detected in HI(2) (106 +/- 10 s versus 108 +/- 9 s). The results indicate that an increased Na(+),K(+) pump expression per se is of importance for thigh K(+) reuptake at the onset of low and moderate intensity exercise, but less important during high intensity exercise.