Cheyne-Stokes respiration in patients hospitalised for heart failure

BackgroundPrevious studies showing a strong relationship between Cheyne-Stokes respiration and the severity of left ventricular systolic dysfunction have usually been done in selected patient populations with lower age and a higher proportion of males than the "typical" in-hospital patient with heart failure. The purpose of the present study was test the strength of this relationship in unselected patients admitted to hospital due to decompensated chronic heart failure.MethodsWe evaluated 191 patients (32% women), mean age 73 years, ready for discharge from the heart failure unit in the University Hospital of Malmö, Sweden. The patients underwent echocardiography for determination of left ventricular ejection fraction and left ventricular inner diastolic diameter. A respiratory investigation during sleep was performed the last night before discharge.ResultsWe found that 66% of the patients had Cheyne-Stokes respiration more than 10% of the total recording time. Only 7 (3.6%) of the patients had predominantly obstructive apnoeas. There was a significant but very weak relationship between left ventricular ejection fraction and left ventricular inner diastolic diameter on one hand and Cheyne-Stokes respiration on the other. Age was a stronger determinant of Cheyne-Stokes respiration than any of the cardiac or other clinical variables.ConclusionAlthough presence of Cheyne-Stokes respiration indicates left ventricular dysfunction, its severity seems only weakly related to the severity of heart failure. Age was found to be a stronger determinant, which may reflect the underlying age-dependency found also in healthy subjects. Due to age restrictions or other selection criteria, the importance of age may have been underestimated in many previous studies on factors associated with Cheyne-Stokes respiration.     

Influence of Cheyne-Stokes respiration on ventricular response to atrial fibrillation in heart failure.

In subjects with sinus rhythm, respiration has a profound effect on heart rate variability (HRV) at high frequencies (HF). Because this HF respiratory arrhythmia is lost in atrial fibrillation (AF), it has been assumed that respiration does not influence the ventricular response. However, previous investigations have not considered the possibility that respiration might influence HRV at lower frequencies. We hypothesized that Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) would entrain HRV at very low frequency (VLF) in AF by modulating atrioventricular (AV) nodal refractory period and concealed conduction. Power spectral analysis of R-wave-to-R-wave (R-R) intervals and respiration during sleep were performed in 13 subjects with AF and CSR-CSA. As anticipated, no modulation of HRV was detected at HF during regular breathing. In contrast, VLF HRV was entrained by CSR-CSA [coherence between respiration and HRV of 0.69 (SD 0.22) at VLF during CSR-CSA vs. 0.20 (SD 0.19) at HF during regular breathing, P < 0.001]. Comparison of R-R intervals during CSR-CSA demonstrated a shorter AV node refractory period during hyperpnea than apnea [minimum R-R of 684 (SD 126) vs. 735 ms (SD 147), P < 0.001] and a lesser degree of concealed conduction [scatter of 178 (SD 56) vs. 246 ms (SD 72), P = 0.001]. We conclude that CSR-CSA entrains the ventricular response to AF, even in the absence of HF respiratory arrhythmia, by inducing rhythmic oscillations in AV node refractoriness and the degree of concealed conduction that may be a function of autonomic modulation of the AV node.     

Pacing in congestive heart failure

Despite the major advances in medical drug therapy, heart failure remains a syndrome associated with high mortality and morbidity. Biventricular or left ventricular (LV) short atrioventricular (AV) delay pacing is being tested in congestive heart failure patients with left bundle branch block. The aim is to resynchronise the dyscoordinate LV contraction. A number of studies are underway, but it is clear that while some patients respond remarkably, this is highly variable. Accurate identification of patients likely to benefit will be crucial. The mechanism of benefit is unclear. A greater understanding of the physiological consequences of pacing will be necessary to accurately identify these patients.     

Role of endothelins in congestive heart failure

Despite major advances in conventional medical therapy, patients with heart failure continue to experience significant morbidity and mortality. Endothelin-1 (ET-1) is a potent vasocontrictor and mitogenic peptide that is activated in heart failure. There is increasing experimental and clinical evidence in support of an important role of ET-1 in the pathophysiology of heart failure. Manipulation of the activity of ET-1, especially using endothelin receptor blockers, has allowed for the further elucidation of the role of this neurohormonal system and development of novel therapeutic strategies in heart failure. Published clinical studies of these agents to date have involved relatively small numbers of patients with severe heart failure, followed for a relatively short period of time, and have mainly examined surrogate endpoints. Large-scale trials that address to hard clinical outcomes are ongoing and their results forthcoming. A key question that remains concerns whether selective ETA or dual ETA-ETB receptor blockade will be more effective.     

Models of Cheyne-Stokes respiration with cardiovascular pathologies

Cheyne-Stokes respiration (CSR) is a periodic breathing pattern, characterized by short intervals of very little or no breathing (apnea), each followed by an interval of very heavy breathing (hyperpnea). This work presents a new compartmental model of the human cardio-respiratory system, simulating the factors that determine the concentrations of carbon dioxide in the compartments of the cardiovascular system and the lungs. The parameter set on which a Hopf bifurcation gives birth to stable CSR oscillations has been determined. The model predicts that the onset of CSR oscillations may result from an increase in any of: ventilation-perfusion ratio, feedback control gain, transport delay, left heart volume, lung congestion, or cardiovascular efficiency. The model is employed to investigate the relationship between CSR and serious cardiovascular pathologies, such as congestive heart failure and encephalitis, as well as the effects of acclimatization to higher altitudes. In all cases, the model is consistent with medical observations.     

Temperature-dependent skeletal muscle dysfunction in rats with congestive heart failure.

Abnormalities in the excitation-contraction coupling of slow-twitch muscle seem to explain the slowing and increased fatigue observed in congestive heart failure (CHF). However, it is not known which elements of the excitation-contraction coupling might be affected. We hypothesize that the temperature sensitivity of contractile properties of the soleus muscle might be altered in CHF possibly because of alterations of the temperature sensitivity of intracellular Ca(2+) handling. We electrically stimulated the in situ soleus muscle of anesthetised rats that had 6-wk postinfarction CHF using 1 and 50 Hz and using a fatigue protocol (5-Hz stimulation for 30 min) at 35, 37, and 40 degrees C. Ca(2+) uptake and release were measured in sarcoplasmic reticulum vesicles at various temperatures. Contraction and relaxation rates of the soleus muscle were slower in CHF than in sham at 35 degrees C, but the difference was almost absent at 40 degrees C. The fatigue protocol revealed that force development was more temperature sensitive in CHF, whereas contraction and relaxation rates were less temperature sensitive in CHF than in sham. The Ca(2+) uptake and release rates did not correlate to the difference between CHF and sham regarding contractile properties or temperature sensitivity. In conclusion, the discrepant results regarding altered temperature sensitivity of contraction and relaxation rates in the soleus muscle of CHF rats compared with Ca(2+) release and uptake rates in vesicles indicate that the molecular cause of slow-twitch muscle dysfunction in CHF is not linked to the intracellular Ca(2+) cycling.