Ali Vazir

A high prevalence of sleep disordered breathing in men with mild symptomatic chronic heart failure due to left ventricular systolic dysfunction

Sleep disordered breathing (SDB) is common in severe chronic heart failure (CHF) and is associated with increased morbidity and mortality. The prevalence of SDB in mild symptomatic CHF is unknown.

Adaptive servo-ventilation in heart failure patients with sleep apnea: A real world study

BACKGROUND Congestive heart failure (CHF) patients often present with obstructive and central sleep apnea occurring concurrently within the same night. This study assessed the efficacy of, and improvements associated with, the use of adaptive servo-ventilation (ASV) in CHF patients with all types of sleep apnea. We hypothesized that ASV would be effective at reducing sleep apnea and improving both cardiac status and quality of life. METHODS Eleven male patients with stable CHF and sleep apnea (apnea/hypopnea index (AHI) >15 events/h) were treated with 6 months optimized ASV and compared to 8 patients not receiving ASV. At baseline, both groups were comparable for New York Heart Association class, left ventricular ejection fraction (LVEF), plasma Brain Natriuretric Peptide (BNP) concentrations and AHI. All patients were receiving optimal medical therapy. RESULTS At 6 months ASV significantly reduced AHI (mean (SD), baseline 49.0 (35.1) v ASV 7.6 (14.6); p=0.001) and LVEF was increased (median (inter-quartile range), treatment group: +5.7 (1.6-9.5) v comparison group: -4.0 (-8.9-+4.6)% respectively; p=0.04) but not BNP (p=0.59). The energy/vitality score of the SF-36 quality of life questionnaire was also improved at 6 months (treatment group: +10 (5-35) v comparison group: -12 (-18-+10); p=0.005). CONCLUSION ASV effectively reduces all types of sleep apnea. Six months of use is associated with improvement in LVEF and aspects of quality of life.

Symptom burden of sleep-disordered breathing in mild-to-moderate congestive heart failure patients

The symptom burden resulting from sleep-disordered breathing (SDB) in patients with mild-to-moderate congestive heart failure (CHF) is unclear. The current authors monitored 24-h activity levels and compared subjective and objective measures of daytime sleepiness in 39 CHF patients, New York Heart Association class 2–3, on optimal medication. A total of 22 patients were classified as SDB (apnoea/hypopnoea index (AHI) median (range) 22.3 (16.6–100) events·h−1), and 17 as no SDB (NoSDB; AHI 3.7 (0–12.3) events·h−1). SDB was defined as AHI ≥15 events·h−1. Patients were assessed by 24-h activity monitoring (actigraphy) for a period of up to 14 days, a single objective sleepiness test (Oxford Sleep Resistance test) and Epworth Sleepiness Scale. The duration of daytime activity was significantly shorter in the SDB group compared with the NoSDB group. The SDB group also had increased time in bed and poorer sleep quality, as shown by the fragmentation index. Objectively the SDB group when compared with the NoSDB group were significantly sleepier, subjectively the groups did not differ. The amount of napping was similar for both groups. Despite the lack of subjective symptoms of daytime sleepiness, congestive heart failure patients with sleep-disordered breathing were objectively sleepier during the day and had reduced daytime activity with longer periods in bed and poorer sleep quality when compared with those without sleep-disordered breathing.

Association between mid-wall late gadolinium enhancement and sudden cardiac death in patients with dilated cardiomyopathy and mild and moderate left ventricular systolic dysfunction

Background: Current guidelines only recommend the use of an implantable cardioverter defibrillator in patients with dilated cardiomyopathy for the primary prevention of sudden cardiac death (SCD) in those with a left ventricular ejection fraction (LVEF) <35%. However, registries of out-of-hospital cardiac arrests demonstrate that 70% to 80% of such patients have an LVEF >35%. Patients with an LVEF >35% also have low competing risks of death from nonsudden causes. Therefore, those at high risk of SCD may gain longevity from successful implantable cardioverter defibrillator therapy. We investigated whether late gadolinium enhancement (LGE) cardiovascular magnetic resonance identified patients with dilated cardiomyopathy without severe LV systolic dysfunction at high risk of SCD. Methods: We prospectively investigated the association between midwall LGE and the prespecified primary composite outcome of SCD or aborted SCD among consecutive referrals with dilated cardiomyopathy and an LVEF ≥40% to our center between January 2000 and December 2011 who did not have a preexisting indication for implantable cardioverter defibrillator implantation. Results: Of 399 patients (145 women, median age 50 years, median LVEF 50%, 25.3% with LGE) followed for a median of 4.6 years, 18 of 101 (17.8%) patients with LGE reached the prespecified end point, compared with 7 of 298 (2.3%) without (hazard ratio [HR], 9.2; 95% confidence interval [CI], 3.9–21.8; P<0.0001). Nine patients (8.9%) with LGE compared with 6 (2.0%) without (HR, 4.9; 95% CI, 1.8–13.5; P=0.002) died suddenly, whereas 10 patients (9.9%) with LGE compared with 1 patient (0.3%) without (HR, 34.8; 95% CI, 4.6–266.6; P<0.001) had aborted SCD. After adjustment, LGE predicted the composite end point (HR, 9.3; 95% CI, 3.9–22.3; P<0.0001), SCD (HR, 4.8; 95% CI, 1.7–13.8; P=0.003), and aborted SCD (HR, 35.9; 95% CI, 4.8–271.4; P<0.001). Estimated HRs for the primary end point for patients with an LGE extent of 0% to 2.5%, 2.5% to 5%, and >5% compared with those without LGE were 10.6 (95% CI, 3.9–29.4), 4.9 (95% CI, 1.3–18.9), and 11.8 (95% CI, 4.3–32.3), respectively. Conclusions: Midwall LGE identifies a group of patients with dilated cardiomyopathy and an LVEF ≥40% at increased risk of SCD and low risk of nonsudden death who may benefit from implantable cardioverter defibrillator implantation. Clinical Trial Registration: URL: http://clinicaltrials.gov. Unique identifier: NCT00930735.

Variation in severity and type of sleep-disordered breathing throughout 4 nights in patients with heart failure

BACKGROUND Over 50% of patients with chronic heart failure (CHF) have sleep-disordered breathing (SDB). Any variation in the type of SDB in CHF will have implications for patient management. Currently there is good evidence for treatment of obstructive sleep apnea (OSA) in CHF with continuous positive airway pressure; however, for central sleep apnea (CSA) the treatment is less clear. AIMS The aim of this study was to investigate the variation in the severity and type of SDB (OSA vs. CSA) throughout 4 consecutive nights in CHF patients with SDB. METHODS Nineteen male CHF patients (mean+/-sd: age 61+/-9 years; left ventricular ejection fraction: 34+/-10% and percent predicted peak VO2: 67+/-19%) underwent cardiorespiratory monitoring in their own home throughout 4 consecutive nights. RESULTS There was minimal variation in apnea-hypopnea index (AHI) throughout 4 nights in CHF patients with SDB [intraclass correlation coefficient (95% confidence interval (CI)): 0.97 (95% CI 0.76 and 0.97)]. Eight patients [42% (95% CI 20% and 64%)] demonstrated a shift in the type of their SDB, from CSA to OSA or vice versa; these patients had significantly smaller neck circumference (group mean+/-sd) 42+/-2 vs. 44+/-2 cm; p=0.04), and had significant variation in the central AHI [intraclass correlation coefficient: 0.51 (95% CI 0.16 and 0.85)]. CONCLUSIONS A single night of cardiorespiratory monitoring is representative of moderate-to-severe SDB in patients with CHF. However, a high proportion of patients shift their type of SDB over 4 nights. These findings may have implications for the management of SDB in CHF.

Ursodeoxycholic acid in patients with chronic heart failure: a double-blind, randomized, placebo-controlled, crossover trial.

OBJECTIVES This study sought to assess the effects of ursodeoxycholic acid (UDCA) on endothelial function and inflammatory markers in patients with chronic heart failure (CHF). BACKGROUND Endothelial dysfunction is commonly observed in patients with CHF, and it contributes to the limitation in exercise capacity that accompanies this condition. Bacterial lipopolysaccharide may trigger proinflammatory cytokine release and promote further endothelial dysfunction. UDCA, a bile acid used in the treatment of cholestatic liver disease, has anti-inflammatory and cytoprotective properties and may contribute to the formation of mixed micelles around lipopolysaccharide. These properties may help to improve peripheral blood flow in patients with CHF. METHODS We performed a prospective, single-center, double-blind, randomized, placebo-controlled crossover study of UDCA in 17 clinically stable male patients with CHF (New York Heart Association functional class II/III, left ventricular ejection fraction <45%). Patients received in random order 500 mg UDCA twice daily for 4 weeks and placebo for another 4 weeks. The primary endpoint was post-ischemic peak peripheral arm blood flow as assessed by strain-gauge plethysmography. RESULTS Sixteen patients completed the study. UDCA was well tolerated in all patients. Compared with placebo, UDCA improved peak post-ischemic blood flow in the arm (+18%, p = 0.038), and a trend for improved peak post-ischemic blood flow in the leg was found (+17%, p = 0.079). Liver function improved: compared with placebo, levels of γ-glutamyl transferase, aspartate transaminase, and soluble tumor necrosis factor α receptor 1 were lower after treatment with UDCA than after placebo (all p < 0.05). There was no change in 6-min walk test or New York Heart Association functional class, and levels of tumor necrosis factor α and interleukin-6 were unchanged or increased compared with placebo. CONCLUSIONS UDCA is well tolerated in patients with CHF. UDCA improves peripheral blood flow and is associated with improved markers of liver function.

Prognostic importance of temporal changes in resting heart rate in heart failure patients: an analysis of the CHARM program

BACKGROUND Resting heart rate (HR) is a predictor of adverse outcome in patients with heart failure (HF). Whether changes in HR over time in patients with chronic HF are also associated with adverse outcome is unknown. We explored the relationship between changes in HR from a preceding visit, time-updated HR (i.e. most recent available HR value from a clinic visit) and subsequent outcomes in patients with chronic HF. METHODS AND RESULTS We studied 7599 patients enrolled in the candesartan in heart failure: assessment of reduction in mortality and morbidity program. We calculated change in HR from the preceding visit and explored its association with outcomes in Cox proportional hazards models, as well the association between time-updated HR and outcome. An increase in HR from preceding visit was associated with a higher risk of all-cause mortality and the composite endpoint of cardiovascular death or hospitalization for HF (adjusted hazard ratio 1.06, 95% confidence intervals, CI: 1.05-1.08, P < 0.001, per 5 b.p.m. higher HR), with lowering of HR being associated with lower risk, adjusting for covariates, including time-updated β-blocker dose and baseline HR. Time-updated resting HR at each visit was also associated with risk (adjusted hazard ratio 1.07, 95% CI: 1.06-1.09; P < 0.001, per 5 b.p.m. higher HR). CONCLUSIONS Change in HR over time predicts outcome in patients with chronic HF, as does time-updated HR during follow-up. These data suggest that frequent outpatient monitoring of HR, and identification of changes over time, possibly with remote technologies, may identify patients with HF who may be at increased risk of rehospitalization or death.

Can heart rate variation rule out sleep-disordered breathing in heart failure?

In patients with obstructive sleep apnoea (OSA), the very low frequency power spectral density index (VLFI) derived from analysis of heart rate correlates with the severity of obstructive apnoeas. VLFI is also associated with Cheyne–Stokes respiration/central sleep apnoea (CSR/CSA) in congestive heart failure (CHF). The present authors have tested the hypothesis that per cent VLFI, derived from a standard Holter ECG recording, can be used to detect the presence of OSA and CSR/CSA in patients with mild-to-moderate CHF. In total, 60 CHF patients underwent polysomnography with monitoring of heart rate. Data from 33 patients were analysed for per cent VLFI. Of the 60 patients, 27 were excluded due to atrial fibrillation, extensive pacing or frequent ventricular extra systoles. Receiver operator characteristic curves were constructed to establish the per cent VLFI that would optimally identify the presence or absence of sleep-disordered breathing. Using an apnoea–hypopnoea index >20 events·h−1 and setting the per cent VLFI at 2.23% yielded a sensitivity of 85%, specificity of 65%, positive predictive value of 61% and a negative predictive value of 87%. The latter increased to 100% when using an apnoea–hypopnoea cut-off of 30 events·h−1. In conclusion, these results suggest that spectral analysis of heart rate may be useful as a “rule-out test” for sleep-disordered breathing in patients with mild-to-moderate congestive heart failure.

Overnight changes in the cerebral vascular response to isocapnic hypoxia and hypercapnia in healthy humans: Protection against stroke

Background and Purpose— The reduction in hypercapnic cerebral vascular reactivity that occurs in the morning after sleep is associated with an increased risk of cerebral ischemia and stroke. It is not known if the cerebral vascular response to hypoxia is similarly reduced in the morning, but such a reduction could be considered a further risk factor for cerebral vascular disease. Methods— To test if the cerebral vascular response to hypoxia is reduced in the morning, the overnight changes in the left middle cerebral artery velocity (MCAV) in response to isocapnic hypoxia (IH) and hypercapnia before and after a normal night sleep were determined in 18 individuals. Results— From evening to morning, hypercapnic cerebral vascular reactivity decreased significantly (evening 2.0±0.4, morning 1.3±0.2 cm/sec/mm Hg; P<0.05); in contrast, the increase in MCAV in response to IH (−10% SaO2) was unchanged (evening 9.0±1.4, morning 8.7±2.2%; P>0.05). Conclusions— Our findings indicate that substantial differences exist in the regulation of the cerebral circulation in response to hypoxia and hypercapnia on waking from sleep. An intact cerebral vascular response to IH, during this time period, could be interpreted as a protective mechanism against cerebral ischemia and stroke; this is of particular relevance to patients with obstructive sleep apnea who arouse from sleep during hypoxia.

Resolution of central sleep apnoea following implantation of a left ventricular assist device.

Central sleep apnoea (CSA) occurs in up to 40% of patients with chronic heart failure (CHF). It is thought to be a consequence of CHF and is associated with an accelerated decline in cardiac function, and increased morbidity and mortality. The optimal treatment of CSA remains unclear. Resolution of CSA has been reported after cardiac transplantation. We report the first case of resolution of CSA 10 months following implantation of a permanent Jarvik 2000 left ventricular assist device (LVAD). The correction of CSA after implantation of the LVAD was associated with improvements in symptoms, exercise capacity, renal function, and increased arterial carbon dioxide levels at rest during wakefulness and also reduction in brain natriuretic peptide.