Differential prognostic impact of resting heart rate in older compared with younger patients with chronic heart failure--insights from TIME-CHF.

BACKGROUND: There is little information regarding the prognostic role of resting heart rate (HR) in older compared with younger patients with chronic heart failure (HF). METHODS AND RESULTS: In patients enrolled in the Trial of Intensified Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) with sinus rhythm, effects of baseline HR (≥70 vs <70 beats/min [bpm]) on 18-month outcomes were compared between older (≥75 years; n = 186) and younger (<75 years; n = 141) patients. Older patients with lower (61 ± 6 bpm) and higher (83 ± 9 bpm) HR had similar left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) functional class, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and survival and HF hospitalization-free survival. In contrast, younger patients with higher HR (81 ± 7 bpm) had higher NT-proBNP and NYHA functional class, lower LVEF, and a higher risk of death (hazard ratio 4.01 [95% confidence interval (CI) 1.17 -13.69]; P = .02) and death or HF hospitalization (hazard ratio 2.35 [95% CI 1.01-5.50]; P = .04) than those with lower HR (62 ± 5 bpm), with the association between higher HR and survival remaining significant after adjustment for NYHA functional class, LVEF, and NT-proBNP. CONCLUSIONS: In contrast to HF patients aged <75 years, we found no association between HR and worse outcomes in HF patients aged ≥75 years.

Midregional pro-adrenomedullin and copeptin: exercise kinetics and association with the cardiopulmonary exercise response in comparison to B-type natriuretic peptide.

PURPOSE: Midregional pro-adrenomedullin (MR-proADM) and C-terminal pro-vasopressin (copeptin) are novel biomarkers providing prognostic information in various settings. We aimed to (1) assess the kinetics of MR-proADM and copeptin during cardiopulmonary exercise testing (CPET); (2) assess the relationship of MR-proADM and copeptin measured at rest with peak oxygen consumption (peak VO2) and other key CPET parameters; (3) compare this relationship to that of B-type natriuretic peptide (BNP). METHODS: In 162 patients undergoing symptom-limited CPET for evaluation of exercise intolerance, MR-proADM, copeptin, and BNP were measured at rest and peak exercise. RESULTS: There was a significant rise in copeptin and BNP (p < 0.001) but not in MR-proADM (p = 0.60) from rest to peak exercise. MR-proADM (r = -0.57; p < 0.001) and BNP (r = -0.49; p < 0.001) but not copeptin were significantly and inversely related to peak VO2. MR-proADM was inversely correlated to the percentage of predicted heart rate achieved and peak oxygen pulse and directly related to the peak ventilation/carbon dioxide production relationship, the physiological dead space-to-tidal volume ratio, and the alveolo-arterial oxygen gradient (p ≤ 0.01 for all), and these associations were at least as strong as for BNP. In contrast, copeptin was not significantly related to any of these parameters (p > 0.05 for all). CONCLUSION: In contrast to BNP and copeptin, MR-proADM is not immediately affected by a maximal exercise test. MR-proADM but not copeptin is at least as good an indicator of low peak VO2 and CPET parameters reflecting an impaired cardiac output reserve, ventilatory efficiency and diffusion capacity as BNP, and thereby a global cardiopulmonary stress marker.

Exercise training reverses exertional oscillatory ventilation in heart failure patients.

Exertional oscillatory ventilation (EOV) is an ominous prognostic sign in chronic heart failure (CHF), but little is known about the success of specific therapeutic interventions. Our aim was to study the impact of an exercise training on exercise capacity and cardiopulmonary adaptation in stable CHF patients with left ventricular systolic dysfunction and EOV. 96 stable CHF patients with EOV were included in a retrospective analysis (52 training versus 44 controls). EOV was defined as follows: 1) three or more oscillatory fluctuations in minute ventilation (V'(E)) during exercise; 2) regular oscillations; and 3) minimal average ventilation amplitude ≥5 L. EOV disappeared in 37 (71.2%) out of 52 patients after training, but only in one (2.3%) out of 44 without training (p<0.001). The decrease of EOV amplitude correlated with changes in end-tidal carbon dioxide tension (r= -0.60, p<0.001) at the respiratory compensation point and V'(E)/carbon dioxide production (V'(CO(2))) slope (r=0.50, p<0.001). Training significantly improved resting values of respiratory frequency (f(R)), V'(E), tidal volume (V(T)) and V'(E)/V'(CO(2)) ratio. During exercise, V'(E) and V(T) reached significantly higher values at the peak, while f(R) and V'(E)/V'(CO(2)) ratio were significantly lower at submaximal exercise. No change was noted in the control group. Exercise training leads to a significant decrease of EOV and improves ventilatory efficiency in patients with stable CHF.

Electrodynamics of clinical hypnosis.

This paper reconstructs and attempts to verify hypotheses made by Leonard Ravitz, Ernest L. Rossi, and Milton H. Erickson, during their research on the influence of hypnosis on the human electromagnetic field. Original charts measured electrodynamic voltage differences of 44 subjects. These voltage differences from Ravitz, Erickson and Rossi's research were digitalized and analyzed with statistical software to check the significance of four hypotheses about ways hypnosis influences the individual's electrodynamic recording. The results of this analysis of the magnitude of the subject's electrodynamic tracing were: (1) there was a statistically significant difference between the prehypnotic condition and hypnosis; (2) there was a statistically significant difference between hypnosis and posthypnotic condition; (3) there was no significant difference between posthypnotic and prehypnotic condition; and (4) there was a statistically significant correlation between an induction of catalepsy and alterations in the electrodynamic tracing. The significance of these findings is discussed with applications to Rossi's 4-Stage Creative Cycle.

Influence of exertional oscillatory ventilation on exercise performance in heart failure.

BACKGROUND: Exertional oscillatory ventilation (EOV) in heart failure may potentiate the negative effects of low cardiac output and high ventilation on exercise performance. We hypothesized that the presence of EOV might, per se, influence exercise capacity as evaluated by maximal cardiopulmonary exercise test. METHODS AND RESULTS: We identified 78 severe chronic heart failure patient pairs with and without EOV. Patients were matched for sex, age and peak oxygen consumption (VO2). Patients with EOV showed, for the same peak VO2, a lower workload (WL) at peak (DeltaWatts=5.8+/-23.0, P=0.027), a less efficient ventilation (higher VE/VCO2 slope: 38.0+/-8.3 vs. 32.8+/-6.3, P<0.001), lower peak exercise tidal volume (1.49+/-0.36 L vs. 1.61+/-0.46 L, P=0.015) and higher peak respiratory rate (34+/-7/min vs. 31+/-6/min, P=0.002). In 33 patients, EOV disappeared during exercise, whereas in 45 patients EOV persisted. Fifty percent of EOV disappearing patients had an increase in the VO2/WL relationship after EOV regression, consistent with a more efficient oxygen delivery to muscles. No cardiopulmonary exercise test parameter was associated with the different behaviour of VO2/WL. CONCLUSION: The presence of EOV negatively influences exercise performance of chronic heart failure patients likely because of an increased cost of breathing. EOV disappearance during exercise is associated with a more efficient oxygen delivery in several cases.

Anticoagulation practices in adults with congenital heart disease and atrial arrhythmias in Switzerland.

BACKGROUND: In adults with congenital heart disease (CHD) and atrial arrhythmias, recommendations for thromboprophylaxis are vague and evidence is lacking. We aimed to identify factors that influence decision-making in daily practice. METHODS: From the Swiss Adult Congenital HEart disease Registry (SACHER) we identified 241 patients with either atrial fibrillation (Afib) or atrial flutter/intraatrial reentrant tachycardia (Aflut/IART). The mode of anticoagulation was reviewed. Logistic regression models were used to assess factors that were associated with oral anticoagulation therapy. RESULTS: Compared with patients with Aflut/IART, patients with Afib were older (51 ± 16.1 vs 37 ± 16 years, P < .001) and had a higher CHA2 DS2 -VASc (P < .001) and HAS-BLED scores (P = .005). Patients with Afib were more likely on oral anticoagulation than patients with Aflut/IART (67% vs 43%, P < .001). In a multivariate logistic regression model, age [odds ratio (OR) 1.03 per year, 95%CI (1.01-1.05), P = .019], atrial fibrillation [OR 2.75, 95%CI (1.30-5.08), P = .007], non-paroxysmal atrial arrhythmias [OR 5.33, 95%CI (2.21-12.85)], CHA2 DS2 -VASc-Score >1 [OR 2.93, 95%CI (1.87-4.61), P < .001], and Fontan palliation [OR 17.5, 95%CI (5.57-54.97), P < .001] were independently associated with oral anticoagulation treatment, whereas a HAS-BLED score >1 was associated with absence of thromboprophylaxis [OR 0.32, 95%CI (0.17-0.60), P < .001]. CONCLUSIONS: In this multicenter study, age, type, and duration of atrial arrhythmias, CHA2 DS2 -VASc and HAS-BLED scores as well as a Fontan palliation had an impact on the use of thromboprophylaxis in adult CHD patients with atrial arrhythmias. In daily practice, anticoagulation strategies differ between patients with Afib and those with Aflut/IART. Prospective observational studies are necessary to clarify whether this attitude is justified.

Patterns of Incidence Rates of Cardiac Complications in Patients With Congenital Heart Disease.

BACKGROUND: This study aimed to evaluate age at the first onset of cardiac complications and variation of frequency of complications between different congenital heart defects. METHODS: The analysis included participants of the Swiss Adult Congenital Heart Disease Registry (SACHER). For this study, cardiac complications up to the time of inclusion in SACHER were analysed. Complications included atrial fibrillation, atrial flutter, supraventricular tachycardia, ventricular tachycardia, complete heart block, heart failure, stroke, endocarditis, myocardial infarction, and pulmonary hypertension. Incidence rates (IR; incidence rate per 1000 patient-years) for different age categories and diagnosis groups were analysed. RESULTS: Of 2731 patients (55% male, mean age 34 ± 14 years, 92,349 patient-years), a total of 767 (28%) had experienced at least 1 cardiac complication. The majority of complications (550; 72%) occurred in adulthood (> 18 years). Apart from perioperative stroke (IR: 1.77 in age group ≤ 4 years) and complete heart block (IR: 2.36 in age group ≤ 4 years), IR were much lower in childhood (IR < 1 for all complications between 5 and 17 years). Incidence of cardiac complications increased during adult life with highest IR for atrial fibrillation and atrial flutter in the age group ≥ 50 years (IR: 17.6 and 9.7, respectively). There were important variations of the distribution of complications among different diagnosis groups. CONCLUSIONS: Cardiac complications are frequent in congenital heart disease. Apart from perioperative stroke and complete heart block, IR are low in childhood but the incidence increases during adult life. These data underscore the need of lifelong follow-up and may help for better allocation of resources maintaining follow-up.

Prognostic Value of the Change in Heart Rate From the Supine to the Upright Position in Patients With Chronic Heart Failure.

BACKGROUND: The prognostic value of the change in heart rate from the supine to upright position (∆HR) in patients with chronic heart failure (HF) is unknown. METHODS AND RESULTS: ∆HR was measured in patients enrolled in the Trial of Intensified Medical Therapy in Elderly Patients with Congestive Heart Failure (TIME-CHF) who were in sinus rhythm and had no pacemaker throughout the trial (n=321). The impact of ∆HR on 18-month outcome (HF hospitalization-free survival) was assessed. In addition, the prognostic effect of changes in ∆HR between baseline and month 6 on outcomes in the following 12 months was determined. A lower ∆HR was associated with a higher risk of death or HF hospitalization (hazard ratio 1.79 [95% confidence interval {95% CI} 1.19-2.75] if ∆HR ≤3 beats/min [bpm], P=0.004). In the multivariate analysis, lower ∆HR remained an independent predictor of death or HF hospitalization (hazard ratio 1.75 [95% CI, 1.18-2.61] if ∆HR ≤3 bpm, P=0.004) along with ischemic HF etiology, lower estimated glomerular filtration rate, presence and extent of rales, and no baseline ß-blocker use. In patients without event during the first 6 months, the change in ∆HR from baseline to month 6 predicted death or HF hospitalization during the following 12 months (hazard ratio=2.13 [95% CI 1.12-5.00] if rise in ∆HR <2 bpm; P=0.027). CONCLUSIONS: ∆HR as a simple bedside test is an independent prognostic predictor in patients with chronic HF. ∆HR is modifiable, and changes in ∆HR also provide prognostic information, which raises the possibility that ∆HR may help to guide treatment. CLINICAL TRIAL REGISTRATION INFORMATION: URL: www.isrctn.org. Unique identifier: ISRCTN43596477.

Chronotropic incompetence predicts impaired response to exercise training in heart failure patients with sinus rhythm.

BACKGROUND: In most patients with chronic heart failure (CHF), endurance training improves exercise capacity. However, some patients do not respond favourably. The purpose of this study was to explore the reasons of non-response and to determine their predictive value. METHODS: We studied a cohort of 120 consecutive CHF patients with sinus rhythm (mean age 57 ± 12 years, ejection fraction 29.3 ± 9.9%, peak VO2 17.3 ± 5.1 ml/min/kg), participating in a 3-month outpatient cardiac rehabilitation programme. Responders were defined as subjects who improved peak VO2 by more than 5%, work load by more than 10%, or VE/VCO2 slope by more than 5%. Subjects who did not fulfil at least one of the above criteria were characterized as non-responders. Multivariate regression analyses were performed to identify parameters that were predictive for a response. Receiver operating characteristic (ROC) analyses were performed for predictive parameters to identify thresholds for response or non-response. RESULTS: Multivariate regression analyses revealed heart rate (HR) reserve, HR recovery at 1 min, and peak HR as significant predictors for a positive training response. ROC curves revealed the optimal thresholds separating responders from non-responders at less than 30 bpm for HR reserve, less than 6 bpm for HR recovery and less than 101 bpm for peak HR. CONCLUSIONS: The presence of impaired chronotropic competence is a major predictor of poor training response in CHF patients with sinus rhythm.

Heart rate at discharge and long-term prognosis following percutaneous coronary intervention in stable and acute coronary syndromes--results from the BASKET PROVE trial.

BACKGROUND: Elevated heart rate (HR) is associated with mortality in a number of heart diseases. We examined the long-term prognostic significance of HR at discharge in a contemporary population of patients with stable angina (SAP), non-ST-segment elevation acute coronary syndromes (NSTE-ACS), and ST-segment elevation myocardial infarction (STEMI) revascularized with percutaneous coronary intervention (PCI). METHODS: Patients from the BASKET-PROVE trial, an 11-center randomized all-comers trial comparing bare-metal and drug-eluting stenting in large coronary vessels, were included. Discharge HR was determined from a resting ECG. Long-term outcomes (7 days to 2 years) were evaluated for all-cause mortality and cardiovascular death and non-fatal myocardial infarction. RESULTS: A total of 2029 patients with sinus rhythm were included, 722 (35.6%) SAP, 647 (31.9%) NSTE-ACS, and 660 (32.5%) STEMI. Elevated discharge HR was associated significantly with all-cause mortality: when compared to a reference of <60 beats per minute (bpm), the adjusted hazard ratios were (95% CI) 4.5 (1.5-13.5, p=0.006) for 60-69 bpm, 3.8 (1.2-11.9, p=0.022) for 70-79 bpm, 4.3 (1.2-15.6, p=0.025) for 80-89 bpm, and 16.9 (5.2-55.0, p<0.001) for >90 bpm. For cardiovascular death/myocardial infarction, a discharge HR >90 bpm was associated with a hazard ratio of 6.2 (2.5-15.5, p<0.001) compared to a HR <60 bpm. No interaction was found for disease presentation, diabetes or betablocker use. CONCLUSION: In patients revascularized with PCI for stable angina or acute coronary syndromes an elevated discharge HR was independently associated with poor prognosis. Conversely, a HR <60 bpm at discharge was associated with a good long-term prognosis irrespective of indication for PCI.