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Biomedical subjects

Richard Sutton

Publications and source records attributed to Richard Sutton.

At least 19 recordsLinked to original sources
PubMed2006

Limitations of the New York Heart Association functional classification system and self-reported walking distances in chronic heart failure.

BACKGROUND: Two ways to evaluate the symptoms of heart failure are the New York Heart Association (NYHA) classification and asking patients how far they can walk (walk distance). The NYHA system is commonly used, although it is not clear how individual clinicians apply it. AIM: To investigate how useful these measures are to assess heart failure and whether other questions might be more helpful. METHODS: 30 cardiologists were asked what questions they used when assessing patients with heart failure. To assess interoperator variability, two cardiologists assessed a series of 50 patients in classes II and III using the NYHA classification. 45 patients who had undergone cardiopulmonary testing were interviewed using a specially formulated questionnaire. They were also asked how far they could walk before being stopped by symptoms, and then tested on their ability to estimate distance. RESULTS: The survey of cardiologists showed no consistent method for assessing NYHA class and a literature survey showed that 99% of research papers do not reference or describe their methods for assigning NYHA classes. The interoperator variability study showed only 54% concordance between the two cardiologists. 70% of cardiologists asked patients for their walk distance; however, this walk distance correlated poorly with actual exercise capacity measured by cardiopulmonary testing (rho = 0.04, p = 0.82). CONCLUSION: No consistent method of assessing NYHA class is in use and the interoperator study on class II and class III patients gave a result little better than chance. Some potential questions are offered for use in assessment. Walking distance, although frequently asked, does not correlate with formally measured exercise capacity, even after correction for patient perception of distance, and has never been found to have prognostic relevance. Its value is therefore doubtful.

Activities of Daily Living↗
PubMed2006

Heart rate response during exercise predicts survival in adults with congenital heart disease.

OBJECTIVES: To assess the prognostic value of heart rate response to exercise in adult congenital heart disease (ACHD) patients. BACKGROUND: An abnormal heart rate response to exercise is related to autonomic dysfunction and may have prognostic implications in ACHD. METHODS: We identified 727 consecutive ACHD patients (mean age [+/- SD] 33 +/- 13 years) with varying diagnoses and without pacemakers. Peak oxygen consumption (peak VO2), resting heart rate, and the increase in heart rate from resting level to peak exercise ("heart rate reserve") were measured. We also quantified the decrease in heart rate ("heart rate recovery") after cessation of exercise. RESULTS: During a median follow-up of 28 months, 38 patients died. Lower values of heart rate reserve, peak heart rate, heart rate recovery, and peak VO2 (p < 0.01 for each) were associated with increased mortality in univariate analysis. Furthermore, heart rate reserve predicted mortality independently of antiarrhythmic therapy, functional class, and peak VO2. Stratifying patients by diagnostic groups revealed that a lower heart rate reserve was also associated with a greater risk of death in patients with complex anatomy, Fontan circulation, and tetralogy of Fallot (p < 0.05 for each). CONCLUSIONS: An abnormal heart rate response to exercise identifies ACHD patients with a higher risk of mortality in the midterm, even after accounting for antiarrhythmic medication and exercise capacity. Heart rate reserve is a simple and inexpensive way to identify ACHD patients at higher mortality risk.

Adult↗
PubMed2006

Lack of correlation between the responses to tilt testing and adenosine triphosphate test and the mechanism of spontaneous neurally mediated syncope.

AIMS: We prospectively correlated the results of tilt testing (TT) and adenosine triphosphate test (ATP) with the findings observed during a spontaneous syncopal relapse by means of an implantable loop recorder (ILR) in patients with a clinical diagnosis of neurally mediated syncope. METHODS AND RESULTS: We included patients with three or more clinically severe syncopal episodes in the last 2 years without significant electrocardiographic and cardiac abnormalities. Patients with orthostatic hypotension and carotid sinus syncope were excluded. After ILR implantation, patients were followed until the first documented syncope. Among 392 enrolled patients, 343 underwent TT, which was positive in 164 (48%), and 180 ATP test, which was positive in 53 (29%). Syncope was documented by ILR in 106 (26%) patients after a median of 3 months. Patients with positive and negative TT had similar baseline characteristics, syncopal recurrence rate, and mechanism of syncope, but those with positive TT had more frequently no or slight rhythm variations during spontaneous syncope (45 vs. 21%, P=0.02). An asystolic pause was more frequently found during spontaneous syncope than during TT (45 vs. 21%, P=0.02), but there was a trend for those with an asystolic response during TT also to have an asystolic response during spontaneous syncope (75 vs. 37%, P=0.1). Patients with positive ATP test responses showed syncopal recurrence rates and mechanism of syncope similar to those with negative ATP tests. CONCLUSION: In patients with neurally mediated syncope, clinical characteristics, outcome, and mechanism of syncope are poorly correlated and not predicted by the results of TT and ATP test. Therefore, these tests are of little or no value in guiding specific therapy.

Adenosine Triphosphate↗
PubMed2006

Early application of an implantable loop recorder allows effective specific therapy in patients with recurrent suspected neurally mediated syncope.

AIMS: This prospective multicentre observational study assessed the efficacy of specific therapy based on implantable loop recorder (ILR) diagnostic observations in patients with recurrent suspected neurally mediated syncope (NMS). METHODS AND RESULTS: Patients with three or more clinically severe syncopal episodes in the last 2 years without significant electrocardiographic and cardiac abnormalities were included. Orthostatic hypotension and carotid sinus syncope were excluded. After ILR implantation, patients were followed until the first documented syncope (Phase I). The ILR documentation of this episode determined the subsequent therapy and commenced Phase II follow-up. Among 392 patients, the 1-year recurrence rate of syncope during Phase I was 33%. One hundred and three patients had a documented episode and entered Phase II: 53 patients received specific therapy [47 a pacemaker because of asystole of a median 11.5 s duration and six anti-tachyarrhythmia therapy (catheter ablation: four, implantable defibrillator: one, anti-arrhythmic drug: one)] and the remaining 50 patients did not receive specific therapy. The 1-year recurrence rate in 53 patients assigned to a specific therapy was 10% (burden 0.07 +/- 0.2 episodes per patient/year) compared with 41% (burden 0.83 +/- 1.57 episodes per patient/year) in the patients without specific therapy (80% relative risk reduction for patients, P = 0.002, and 92% for burden, P = 0.002). The 1-year recurrence rate in patients with pacemakers was 5% (burden 0.05 +/- 0.15 episodes per patient/year). Severe trauma secondary to syncope relapse occurred in 2% and mild trauma in 4% of the patients. CONCLUSION: A strategy based on early diagnostic ILR application, with therapy delayed until documentation of syncope allows a safe, specific, and effective therapy in patients with NMS.

Adult↗
PubMed2006

Mechanism of cardiac output gain from cardiac resynchronization therapy in patients with coronary artery disease or idiopathic dilated cardiomyopathy.

The mechanisms underlying cardiac resynchronization therapy have consistently been studied at rest and remain ill defined. Peak stress total isovolumic time (t-IVT) is a major determinant of cardiac output (CO) in chronic heart failure. In this study, pharmacologic stress was used to assess the effects of atrioventricular (AV) delay shortening and ventricular resynchronization elements of cardiac resynchronization therapy. Thirty patients undergoing cardiac resynchronization therapy were studied <6 months after implantation. t-IVT and CO were measured during native activation (left bundle branch block), AV delay shortening (right ventricular dual-chamber pacing), and full resynchronization (atrio-biventricular pacing). Full resynchronization shortened peak stress t-IVT by 9.4 +/- 6.2 s/min (p <0.001) and increased peak stress CO by 0.9 +/- 0.4 L/min (p <0.001), with the effects in individual patients showing a large correlation (r = -0.64, p <0.001). In contrast, simple AV delay shortening did not shorten peak stress t-IVT nor increase peak stress CO, nor was CO at rest affected by full resynchronization or AV delay shortening. Of all measurements during native activation, the best predictor of gain in peak stress CO from full resynchronization was peak stress t-IVT (r = 0.75, p <0.001), with every 5 s/min increment in peak stress t-IVT during native activation predicting a 6% gain in peak stress CO. No conventional measures during native activation at rest or during stress (including QRS duration, the Tei index, tissue Doppler intraventricular delay, and t-IVT at rest) added significant additional information. In conclusion, only during stress does resynchronization consistently increase CO. Second, little of this increment in CO is achieved by AV delay shortening alone. Third, under native activation, long t-IVT during peak stress is the single best predictor of resynchronization-mediated increment in peak stress CO.

Aged↗
PubMed2006

Augmented cancer resistance and DNA damage response phenotypes in PPM1D null mice.

The p53-induced serine/threonine phosphatase, protein phosphatase 1D magnesium-dependent, delta isoform (PPM1D) (or wild-type p53-induced phosphatase 1 (Wip1)), exhibits oncogenic activity in vitro and in vivo. It behaves as an oncogene in rodent fibroblast transformation assays and is amplified and overexpressed in several human tumor types. It may contribute to oncogenesis through functional inactivation of p53. Here, we show that the oncogenic function of PPM1D is associated with its phosphatase activity. While overexpressed PPM1D may be oncogenic, PPM1D null mice are resistant to spontaneous tumors over their entire lifespan. This cancer resistance may be based in part on an augmented stress response following DNA damage. PPM1D null mice treated with ionizing radiation display increased p53 protein levels and increased phosphorylation of p38 MAP kinase, p53, checkpoint kinase 1 (Chk1), and checkpoint kinase 2 (Chk2) in their tissues compared to their wild-type (WT) counterparts. Male PPM1D null mice show a modest reduction in longevity, reduced serum insulin-like growth factor 1 (IGF-1) levels, and reduced body weight compared to WT mice. The PPM1D null mouse phenotypes indicate that PPM1D has a homeostatic role in abrogating the DNA damage response and may regulate aspects of male longevity.

Aging↗
PubMed2005

Chronic heart failure patients with restrictive LV filling pattern have significantly less benefit from cardiac resynchronization therapy than patients with late LV filling pattern.

BACKGROUND: Cardiac resynchronization fails to improve symptoms in up to one third of patients meeting criteria for this treatment, for reasons which are unclear. Indeed, the very mechanism of benefit from resynchronization is controversial. Resynchronization may work by improving ventricular filling: we tested the hypothesis that benefit from resynchronization depends on filling pattern. METHODS AND RESULTS: We assessed symptoms (NYHA class) and LV filling of 40 patients with chronic heart failure and prolonged QRS who underwent resynchronization. Fifteen had restrictive filling pattern (E velocity>or=1.0 m/s, E/A ratio>1 and E wave deceleration time<or=140 ms) and 25 had late filling pattern (single isolated A wave or summation wave filling in late diastole). At 6 months, the patients with restrictive filling failed to show the improvements observed in those with late filling. They failed to reduce NYHA class (DeltaNYHA: 27% improved one class, 66% unchanged, 7% worsened one class, P=NS; vs. 8% improved two classes, 72% improved one class and 20% unchanged, P<0.001; difference between groups, P<0.001). They failed to reduce LV end-diastolic dimension (DeltaLVEDD -0.04 cm, P=NS; vs. -0.6, P<0.001; difference between groups, P<0.05) or end-systolic dimension (DeltaLVESD -0.01 cm, P=NS; vs. -0.6, P<0.001; difference between groups, P<0.05). They failed to improve cardiac cycle efficiency (Deltatotal isovolumic [wasted] time 2.1 s/min, P=NS; vs. -5.4 s/min; difference between groups, P<0.001). CONCLUSION: Among patients routinely eligible for resynchronization, those with restrictive filling may show significantly less (and possibly no) improvement in symptom class and ventricular dimensions after resynchronization. Their failure to improve cardiac cycle efficiency may account for their attenuated clinical benefit.

Aged↗
PubMed2005

Unconscious confusion--a literature search for definitions of syncope and related disorders.

BACKGROUND: Imprecise definitions of syncope and related conditions appear common in the medical literature. To investigate the scope of the problem we systematically searched for definitions in high-ranking medical journals. METHODS: Literature review of articles on 'syncope', 'neurocardiogenic syncope', 'neurally mediated syncope', 'orthostatic intolerance', and 'orthostatic hypotension' with these keywords in the title, mainly published in the ten journals with the highest impact in the fields of cardiology, internal medicine, and neurology. RESULTS: Syncope, neurocardiogenic syncope, neurally mediated syncope, orthostatic intolerance, and orthostatic hypotension were defined in only 41%, 34%, 26%, 38%, and 48% of papers respectively. Definitions, when given, differed considerably among papers. Orthostatic hypotension was most frequently defined, with an increase in number and consistency of definitions after publication of a consensus in 1996. CONCLUSIONS: Syncope and related conditions proved to be infrequently and inconsistently defined in current medical literature. The lack of consistent terminology is likely to harm medical education, research, and patient care. There is a strong need for a systematic terminology for syncope and related conditions.

Autonomic Nervous System↗
PubMed2005

Proposed electrocardiographic classification of spontaneous syncope documented by an implantable loop recorder.

Uniform data from the literature show that the mechanism of syncope recorded by implantable loop recorder is extremely heterogeneous and a wide variety of rhythm disturbances is recorded at the time of syncope. Therefore, the proposed classification aims to group the observations into homogeneous patterns in order to define an acceptable standard useful for future studies and clinical practice.

Electrocardiography, Ambulatory↗
PubMed2004

Life-years gained from defibrillator implantation: markedly nonlinear increase during 3 years of follow-up and its implications.

BACKGROUND: Although treatment benefit in randomized controlled trials of defibrillators is often summarized by the numbers of lives saved (absolute risk difference), this may not be a good representation of what matters most to patients, namely, the amount of life they should expect to gain from implantation. The estimate of gain in life-years may depend on duration of follow-up. In this study, we examine this dependency. METHODS AND RESULTS: We estimated, from published data of 8 landmark defibrillator trials, the cumulative benefit in life-years gained at time points from 3 months to 3 years. Because the trial populations, clinical status, and prognosis varied widely between studies, we expressed for each study the benefit at each time point as the proportion of benefit at 3 years. The average dependency of the benefit on duration of follow-up was then calculated. We found that the number of life-years gained from 1 device implantation increases with length of follow-up considered. Importantly, this increase is markedly nonlinear. Within the 3-year span addressable, the benefit rises with the square of time (gain infinity t(1.94), R2=0.998, P<0.001). CONCLUSIONS: Measurable benefit from a defibrillator to patients' life spans (life-years gained) is dramatically dependent on the time window over which the benefit is assessed. Because the effort of implantation is front loaded, yet benefit grows with time, the choice of an early time point artificially reduces apparent benefit and artificially increases the apparent number needed to treat to prevent an event. These are useful considerations for the formulation of treatment policy (and even for planning of the follow-up phase of clinical trials).

Clinical Trials as Topic↗
PubMed2004

Syncope.

Syncope is a syndrome consisting of a relatively short period of temporary and self-limited loss of consciousness caused by transient diminution of blood flow to the brain (most often the result of systemic hypotension). Syncope comprises part of a subset of clinical conditions in which loss of consciousness is transient. Other conditions in this group, which are not syncope and should be clearly distinguished from syncope, include, for example, seizure disorders, posttraumatic loss of consciousness, and cataplexy. Recent surveys indicate that syncope accounts for approximately 1% of emergency department visits in Europe, although older reports from the United States placed this number closer to 3%. The reported prevalence of syncope in the population varies: 15% of children before the age of 18 years; 25% of a military population aged 17 to 26 years; 16% and 19%, respectively, in men and women aged 40 to 59 years; and up to 23% in a nursing home population older than 70 years. The highest frequency of syncope occurs in patients with cardiovascular comorbidity and older patients in institutional care settings. The causes of syncope are numerous and, not infrequently, multiple factors may contribute. The diagnostic evaluation is benefited by availability of a detailed medical history and reports of eyewitnesses. In this context, the physician must consider the classification of the causes of syncope, and address the most likely causes first. The principal groups of causes may be summarized as: (1) neurally mediated reflex syncope (eg, vasovagal faint, carotid sinus syndrome); (2) orthostatic (postural) syncope; (3) cardiac arrhythmias; (4) structural cardiac and pulmonary causes; and (5) cerebrovascular disorders (rare). In addition, conditions that may mimic syncope but are not true syncope (eg, psychogenic pseudosyncope) must be considered. Only after a definitive cause is established can appropriate treatment be initiated. In this regard, the syncope evaluation is facilitated by maintaining an organized diagnostic approach. The practitioner should avoid wasteful use of short-term ambulatory electrocardiographic recordings (eg, Holter monitors) and rarely positive neurologic tests (eg, electroencephelography, head magnetic resonance imaging/computed tomography) in the absence of head trauma or evident neurologic signs. In many medical centers the evaluation of patients with syncope is haphazard, and may be substantially enhanced by establishment of a multidisciplinary syncope evaluation unit or team.

Diagnosis, Differential↗
PubMed2004

A randomized, double-blind, placebo-controlled study of permanent cardiac pacing for the treatment of recurrent tilt-induced vasovagal syncope. The vasovagal syncope and pacing trial (SYNPACE).

AIMS: Recently, some studies revealed the efficacy of pacemaker implantation in decreasing recurrences in patients with vasovagal syncope. As these studies were not blinded or placebo-controlled, the benefits observed might have been due to a bias in the assessment of outcomes or to a placebo effect of the pacemaker. We performed a randomized, double-blind, placebo-controlled study in order to ascertain if pacing therapy reduces the risk of syncope relapse. METHODS AND RESULTS: Twenty-nine patients (53 +/- 16 years; 19 women) with severe recurrent tilt-induced vasovagal syncope (median 12 syncopes in the lifetime) and 1 syncopal relapse after head-up tilt testing underwent implantation of a pacemaker, and were randomized to pacemaker ON or to pacemaker OFF. During a median of 715 days of follow-up, 8 (50%) patients randomized to pacemaker ON had recurrence of syncope compared to 5 (38%) of patients randomized to pacemaker OFF (p = n.s.); the median time to first syncope was longer in the pacemaker ON than in pacemaker OFF group, although not significantly so (97 [38-144] vs 20 [4-302] days; p = 0.38). There was also no significant difference in the subgroups of patients who had had a mixed response and in those who had had an asystolic response during head-up tilt testing. CONCLUSION: Our data were unable to show a superiority of active pacing versus inactive pacing in preventing syncopal recurrence in patients with severe recurrent tilt-induced vasovagal syncope.

Cardiac Pacing, Artificial↗
PubMed2003

Age and hemodynamic responses to tilt testing in those with syncope of unknown origin.

OBJECTIVES: We sought to determine whether there are age-related differences in vasovagal syncope. BACKGROUND: In those with suspected vasovagal (neurocardiogenic) syncope, tilt testing demonstrates different hemodynamic responses. These responses may be age related, reflecting differing underlying pathophysiology. METHODS: Using a two-stage tilt protocol with glyceryl trinitrate (GTN) provocation, 505 consecutive syncopal patients were studied. Their baseline characteristics and hemodynamic responses during both early and tilt-induced collapse were analyzed. Hemodynamic responses were classified using the VAsovagal Syncope International Study (VASIS) criteria: mixed, cardioinhibition, severe cardioinhibition/asystole, pure vasodepression, chronotropic incompetence, and excessive heart rate rise. Multivariate regression analyses were performed to determine the associations of the baseline clinical characteristics (including age) and the tilt-induced hemodynamic responses. RESULTS: Thirty-three patients were unable to tolerate tilt testing. Age was independently associated with distinct responses during tilt. Chronotropic incompetence was predicted by increasing age (odds ratio [OR] 1.04, p < 0.0002). Younger age predicted an excessive heart rate rise (OR 0.97, p < 0.0005). Pure vasodepression was more common in the older group (>65 years; OR 29.5, p < 0.0001), whereas severe cardioinhibition was much less common in the older age group (OR 0.18, p < 0.0001). CONCLUSIONS: There appear to be distinct pathophysiologies underlying vasovagal syncope in different age groups. Young people appear to have excessive cardiac and autonomic responses to stress, whereas older patients appear to have a more generalized cardiovascular decline, with attenuated cardiac and autonomic responses to stress.

Adult↗