Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- A Comprehensive Evaluation of Rhythm Monitoring Strategies for the Detection of Atrial Fibrillation Recurrence: Insights From 647 Continuously Monitored Patients and Implications for Monitoring After Therapeutic Interventions
- Implantable Cardioverter-Defibrillators Have Reduced the Incidence of Resuscitation for Out-of-Hospital Cardiac Arrest Caused by Lethal Arrhythmias
- Effect of QRS Duration and Morphology on Cardiac Resynchronization Therapy Outcomes in Mild Heart Failure: Results From the Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) Study
- Low Myocardial Protein Kinase G Activity in Heart Failure With Preserved Ejection Fraction
- MicroRNA-101 Inhibited Postinfarct Cardiac Fibrosis and Improved Left Ventricular Compliance via the FBJ Osteosarcoma Oncogene/Transforming Growth Factor-β1 Pathway
- Determinants and Prognostic Significance of Exercise Pulmonary Hypertension in Asymptomatic Severe Aortic Stenosis
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A Comprehensive Evaluation of Rhythm Monitoring Strategies for the Detection of Atrial Fibrillation Recurrence: Insights From 647 Continuously Monitored Patients and Implications for Monitoring After Therapeutic Interventions
Patient follow-up with either short- or long-duration intermittent rhythm monitoring is significantly inferior to that with continuous rhythm monitoring for the detection of atrial fibrillation (AF) recurrence. Intermittent rhythm monitoring strategies fail to identify AF recurrence in a great proportion of patients at risk. Even with feasible, aggressive intermittent monitoring strategies (such as quarterly 24-hour Holter monitoring), AF recurrence will not be identified in a significant proportion of patients. Because of the low sensitivity of intermittent rhythm monitoring, the results of pharmacological or invasive interventions for AF when evaluated with intermittent monitoring should be considered with caution because chance has an immeasurable effect on the detection of AF recurrence, and thus a great proportion of patients will be misclassified, AF recurrence will be underdiagnosed, and therapeutic success will be overestimated. Novel quantitative and temporal AF characteristics (AF burden, AF density) play a major role in AF recurrence detection with the use of intermittent monitoring strategies and may influence clinical parameters and outcomes in AF patients. For accurate patient management, as well as for the scientific, evidence-based evaluation of AF treatments, continuous rhythm monitoring should be strongly recommended. See p 806.
Implantable Cardioverter-Defibrillators Have Reduced the Incidence of Resuscitation for Out-of-Hospital Cardiac Arrest Caused by Lethal Arrhythmias
The proportion and incidence of patients with out-of-hospital cardiac arrest (OHCA) that are found in ventricular fibrillation (VF) decreased over the last decades. It used to be well over 70% (incidence, 0.3–0.7/1000 inhabitants) and decreased to 25% to 50% (incidence, 0.1–0.3/1000 inhabitants) in a period of 15 to 20 years. The reason for this worldwide decline in VF is not clear. Possible explanations include a changing morbidity pattern from ischemic heart disease with more chronic heart failure, increased use of β-adrenergic receptor blocking drugs, and later arrival on scene by emergency medical services. We investigated the community impact of implantable cardioverter-defibrillators (ICDs) for primary and secondary prevention by comparing OHCA in the periods 1995–1997 when ICD therapy hardly existed to 2005–2008 in the Dutch province of North Holland. We took into consideration that if no ICD had been placed, resuscitation for OHCA would have occurred only in part of the patients who received an appropriate ICD shock. The incidence (per 100 000 inhabitants per year) of VF OHCA decreased from 21.1 to 17.4, and non-VF OHCA increased from 12.2 to 19.4, corresponding with a decline of VF OHCA from 63% to 47%. ICD shocks avoided 1.2 VF OHCA per 100 000 inhabitants per year. Thus, successful ICD shocks explained 33% of the decline in VF OHCA. In a sensitivity analysis, the explained decline ranged from 16% to 63%. Part of the decreased proportion of VF OHCA of all OHCA was explained by an even larger (and unexplained) increase in non-VF OHCA. Nevertheless, other factors must play at least an equal role in the explanation for the observed decline in VF OHCA. See p 815.
Effect of QRS Duration and Morphology on Cardiac Resynchronization Therapy Outcomes in Mild Heart Failure: Results From the Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) Study
Cardiac resynchronization therapy (CRT) decreases mortality, improves functional status, and induces reverse left ventricular remodeling in selected populations with both mild and advanced heart failure. Despite these benefits of CRT, nearly one third of subjects are typically classified as nonresponders. Characteristics of the surface ECG have been shown to be important predictors of response in several previous studies. In the present analysis of the Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) trial, the impact of baseline QRS duration and morphology and the change in QRS duration with pacing on outcomes in mild heart failure with CRT were described. Patients with left bundle-branch block experienced large reductions in left ventricular volumes, whereas patients with non–left bundle-branch block had much smaller decreases. Baseline QRS duration was also a strong predictor of remodeling, with monotonic increases as QRS duration prolonged and no obvious threshold above 120 milliseconds. Similarly, clinical outcomes improved with CRT for left bundle-branch block subjects but not for non–left bundle-branch block subjects, and clinical outcomes increased as QRS duration prolonged. The change in QRS duration with CRT pacing was not an independent predictor of any outcomes after correction for baseline variables. These data indicate that left bundle-branch block and QRS prolongation are markers of reverse remodeling and clinical benefit with CRT in mild heart failure. However, the change in QRS duration with biventricular pacing is not a useful predictor of response independently of the baseline ECG characteristics. Finally, despite the relationship between QRS duration and outcomes, these results do not support the use of any arbitrary QRS duration cutoff >120 to 130 milliseconds for selecting CRT candidates. See p 822.
Low Myocardial Protein Kinase G Activity in Heart Failure With Preserved Ejection Fraction
Large trials testing modern heart failure pharmacotherapy in heart failure with preserved ejection fraction (HFPEF) had a neutral outcome, probably because of failure to address features of myocardial dysfunction specific for heart failure with preserved ejection fraction such as high-diastolic left ventricular stiffness. The latter results not only from myocardial fibrosis, but also from high cardiomyocyte stiffness, which is linked to hypophosphorylation of the cytoskeletal protein titin and corrected by in vitro administration of protein kinase G (PKG). In vivo administration of sildenafil, which raises myocardial PKG activity by inhibiting breakdown of cyclic guanosine monophosphate, similarly improves diastolic left ventricular stiffness in a HFPEF dog model and HFPEF patients with pulmonary hypertension. Because of these findings and the ongoing RELAX trial testing sildenafil in HFPEF, the present study compared PKG activity, its downstream effects, and its upstream controls in left ventricular endomyocardial biopsies of patients with HFPEF, HF with reduced ejection fraction, and aortic stenosis. Patients were free of coronary artery disease, but more HFPEF patients were obese or had diabetes mellitus. The lowest myocardial PKG activity was observed in HFPEF and associated with the highest cardiomyocyte stiffness, the lowest myocardial cyclic guanosine monophosphate concentration, and the highest myocardial nitrosative/oxidative stress. The high prevalence among HFPEF patients of metabolic disorders probably accounted for their high myocardial nitrosative/oxidative stress, which led to high cardiomyocyte stiffness through a cascade of derangements consisting of low cyclic guanosine monophosphate concentration, low PKG activity, and reduced phosphorylation of titin by PKG. Metabolic derangements therefore underlie diastolic left ventricular dysfunction in HFPEF and should be targeted in future HFPEF treatment strategies. See p 830.
MicroRNA-101 Inhibited Postinfarct Cardiac Fibrosis and Improved Left Ventricular Compliance via the FBJ Osteosarcoma Oncogene/Transforming Growth Factor-β1 Pathway
Myocardial infarction caused by coronary artery occlusion is one of the leading causes of sudden death in the world. Interstitial fibrosis, occurring in both infarcted and noninfarcted myocardium, represents a characteristic pathological alteration of postinfarct remodeling and is regarded as a major determinant of the progressive deterioration of ventricular function and reduced ventricular compliance after myocardial infarction. Fibrosis is characterized by excessive deposition of extracellular matrix proteins. Cardiac fibroblasts, accounting for 60% to 70% of the cells in the human heart, are the main source of extracellular matrix protein production. During myocardial infarction, cardiac fibroblasts are activated and produce excessive amount of extracellular matrix proteins, leading to interstitial fibrosis. Tremendous efforts have been devoted to this pathological process to elucidate the molecular mechanisms and to develop novel antifibrotic strategies. MicroRNAs (miRs), endogenous small noncoding RNAs that regulate the expression of genes, have recently been proven to be a novel class of regulators of cardiovascular diseases, including those associated with cardiac fibrosis. In this study, we discovered that downregulation of an miR called miR-101 contributes significantly to cardiac fibrosis in myocardial infarction hearts; forced expression of miR-101 suppresses cardiac fibrosis and improves the impaired cardiac function in postinfarct rats. Our findings reveal the role of miRNA in controlling cardiac fibrosis in myocardial infarction hearts and indicate that miR-101 is a viable therapeutic strategy for cardiac disease associated with fibrosis. It is speculated that administration of miR-101 mimetics should produce antifibrotic actions, thereby retarding structural remodeling and minimizing functional deterioration of the heart under a variety of pathological settings. See p 840.
Determinants and Prognostic Significance of Exercise Pulmonary Hypertension in Asymptomatic Severe Aortic Stenosis
The management and timing of surgery in asymptomatic patients with severe aortic stenosis remain matters of concern. The risks of aortic valve surgery and late complications of prosthesis in such patients need to be balanced against the possible prevention of sudden death and lowering of cardiac mortality. Hence, early elective surgery could be proposed only to well-selected patients considered at high risk of poor outcome. In the present study, 105 consecutive asymptomatic patients with severe aortic stenosis underwent comprehensive resting and exercise stress echocardiography to evaluate the presence of pulmonary hypertension (PHT). The results showed that 55% of asymptomatic patients may develop exercise PHT. Patients with exercise PHT had significantly lower cardiac event-free survival and a markedly higher rate of death than those without exercise PHT. In addition, exercise PHT was associated with poorer outcome independently of demographic and resting echocardiographic data and exercise-induced changes in mean transaortic pressure gradient. Beyond both resting aortic stenosis severity and systolic pulmonary arterial pressure, the assessment of the presence of exercise PHT provided important incremental predictive value. Even in patients with markedly elevated aortic jet velocity, those with exercise PHT depicted a higher risk of reduced cardiac event-free survival. These results strongly support the use of exercise stress echocardiography in the management of asymptomatic severe aortic stenosis. Early elective aortic valve surgery to prevent irreversible left ventricular myocardial damage, diastolic dysfunction, and symptoms could be advised in patients developing exercise PHT. In contrast, asymptomatic patients with no exercise PHT may be conservatively followed up. See p 851.
- © 2012 American Heart Association, Inc.
- Low Myocardial Protein Kinase G Activity in Heart Failure With Preserved Ejection Fraction
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