Subcutaneous furosemide in advanced heart failure: service improvement project.

OBJECTIVES: In severe heart disease, parenteral administration of loop diuretic is often needed. We present clinical outcomes from episodes of care using subcutaneous continuous subcutaneous infusion of furosemide (CSCI-furosemide). METHODS: Retrospective review of service improvement data. The heart failure nurse specialist, supported by the heart failure-palliative care multidisciplinary team, works with the community or hospice staff who administer the CSCI-furosemide. Data collected for consecutive patients receiving CSCI-furosemide included: age, sex, New York Heart Association (NYHA) class, preferred place of care, goal of treatment, infusion-site reactions, and signs and symptoms of fluid retention (including weight and self-reported breathlessness). RESULTS: 116 people (men 86 (66%); mean age 79 years, 49-97; NYHA class 3 (36/116, 31%) or 4 heart failure (80/116, 69%)) received 130 episodes of CSCI-furosemide (average duration 10 days, 1-49), over half in the patient's own home/care home (80/129,; 61%) aiming to prevent hospital admission. 40/129 (31%) were managed in the hospice, and 9 (7.0%) in a community hospital. Average daily furosemide dose was 125 mg (40-300 mg). The goal of treatment was achieved in (119/130, 91.5%) episodes.The median reduction in weight was 4 kg (IQR -7 to -2 kgs, -22 to 9 kgs). Self-reported breathlessness reduced from 8.2 (±1.9) to 5.2 (±1.8). Adverse events occurred in 31/130 (24%) episodes; all but 4/130 (3%, localised skin infection) were mild. CONCLUSIONS: These preliminary data indicate that CSCI-furosemide is safe and effective for people with severe heart failure. An adequately powered randomised controlled trial is indicated.

Oral modified release morphine for breathlessness in chronic heart failure: a randomized placebo-controlled trial.

AIMS: Morphine is shown to relieve chronic breathlessness in chronic obstructive pulmonary disease. There are no definitive data in people with heart failure. We aimed to determine the effectiveness and cost-effectiveness of 12 weeks morphine therapy for the relief of chronic breathlessness in people with chronic heart failure compared with placebo. METHODS AND RESULTS: Parallel group, double-blind, randomized, placebo-controlled, phase III trial of 20 mg daily oral modified release morphine was conducted in 13 sites in England and Scotland: hospital/community cardiology or palliative care outpatients. The primary analysis compared between-group numerical rating scale average breathlessness/24 hours at week 4 using a covariance pattern linear mixed model. Secondary outcomes included treatment-emergent harms (worse or new). The trial closed early due to slow recruitment, randomizing 45 participants [average age 72 (range 39-89) years; 84% men; 98% New York Heart Association class III]. For the primary analysis, the adjusted mean difference was 0.26 (95% confidence interval, -0.86 to 1.37) in favour of placebo. All other breathlessness measures improved in both groups (week 4 change-from-baseline) but by more in those assigned to morphine. Neither group was excessively drowsy at baseline or week 4. There were no between-group differences in quality of life (Kansas) or cognition (Montreal) at any time point. There was no exercise-related desaturation and no change between baseline and week 4 in either group. There was no change in vital signs at week 4. The natriuretic peptide measures fell in both groups but by more in the morphine group [morphine 2169 (1092, 3851) pg/mL vs. placebo 2851 (1694, 5437)] pg/mL. There was no excess serious adverse events in the morphine group. Treatment-emergent harms during the first week were more common in the morphine group; all apart from 1 were ≤ grade 2. CONCLUSIONS: We could not answer our primary objectives due to inadequate power. However, we provide novel placebo-controlled medium-term benefit and safety data useful for clinical practice and future trial design. Morphine should only be prescribed in this population when other measures are unhelpful and with early management of side effects.

Postmortem ICD interrogation in mode of death classification.

BACKGROUND: The definition of sudden death due to arrhythmia relies on the time interval between onset of symptoms and death. However, not all sudden deaths are due to arrhythmia. In patients with an implantable cardioverter defibrillator (ICD), postmortem device interrogation may help better distinguish the mode of death compared to a time-based definition alone. OBJECTIVE: This study aims to assess the proportion of "sudden" cardiac deaths in patients with an ICD that have confirmed arrhythmia. METHODS: We conducted a literature search for studies using postmortem ICD interrogation and a time-based classification of the mode of death. A modified QUADAS-2 checklist was used to assess risk of bias in individual studies. Outcome data were pooled where sufficient data were available. RESULTS: Our search identified 22 studies undertaken between 1982 and 2015 with 23,600 participants. The pooled results (excluding studies with high risk of bias) suggest that ventricular arrhythmias are present at the time of death in 76% of "sudden" deaths (95% confidence interval [CI] 67-85; range 42-88). CONCLUSION: Postmortem ICD interrogation identifies 24% of "sudden" deaths to be nonarrhythmic. Postmortem device interrogation should be considered in all cases of unexplained sudden cardiac death.

Atrial flow dynamics as a determinant of tissue temperature during balloon cryoablation.

Aims: Balloon cryoablation is an accepted method of achieving pulmonary vein isolation for the treatment of atrial fibrillation. The relationship between blood flow in the atrium and cryo energy delivery to the tissue remains poorly understood. Methods and results: Controlled cryoablations were performed in vitro using a pulmonary vein phantom constructed from bovine muscle, providing a 20 mm vein ostium. A temperature sensor was mounted within the 'vein wall' at a 1 mm tissue depth. Apparatus was constructed to assess the effect of incomplete pulmonary venous occlusion causing a leak, simulated atrial stasis, atrial circulation, and mitral regurgitation. Controlled ablations using the 2nd generation 28 mm cryoballoon catheter were repeated three times and mean values compared. Leak volume significantly affected both balloon temperatures and tissue temperatures. Simulated mitral regurgitation (MR) significantly impaired the effectiveness of cryo energy delivery resulting in significantly warmer balloon and tissue temperatures. With high leak volumes and moderate to severe MR there was a marked disparity between the cryoballoon temperature and the tissue temperature of approximately 60 degrees. Balloon warming times varied inversely with both leak volume and simulated MR flow volume. Conclusion: Incomplete venous occlusion and MR result in warmer balloon and tissue temperatures, and shorter balloon warming times, and are likely to significantly impair the effectiveness of cryoablation. Balloon temperature is poor indicator of tissue temperature under higher flow conditions.

Outcomes Related to First-Degree Atrioventricular Block and Therapeutic Implications in Patients With Heart Failure.

The prevalence of first-degree atrioventricular block in the general population is approximately 4%, and it is associated with an increased risk of atrial fibrillation. Cardiac pacing for any indication in patients with first-degree heart block is associated with worse outcomes compared with patients with normal atrioventricular conduction. Among patients with heart failure, first-degree atrioventricular block is present in anywhere between 15% and 51%. Data from cardiac resynchronization therapy studies have shown that first-degree atrioventricular block is associated with an increased risk of mortality and heart failure hospitalization. Recent studies suggest that optimization of atrioventricular delay in patients with cardiac resynchronization therapy is an important target for therapy; however, the optimal method for atrioventricular resynchronization remains unknown. Understanding the role of first-degree atrioventricular block in the treatment of patients with heart failure will improve medical and device therapy.

Subclavian vein pacing and venous pressure waveform measurement for phrenic nerve monitoring during cryoballoon ablation of atrial fibrillation.

AIMS: The phrenic nerves may be damaged during catheter ablation of atrial fibrillation. Phrenic nerve function is routinely monitored during ablation by stimulating the right phrenic nerve from a site in the superior vena cava (SVC) and manually assessing the strength of diaphragmatic contraction. However the optimal stimulation site, method of assessing diaphragmatic contraction, and techniques for monitoring the left phrenic nerve have not been established. We assessed novel techniques to monitor phrenic nerve function during cryoablation procedures. METHODS AND RESULTS: Pacing threshold and stability of phrenic nerve capture were assessed when pacing from the SVC, left and right subclavian veins. Femoral venous pressure waveforms were used to monitor the strength of diaphragmatic contraction. Stable capture of the left phrenic nerve by stimulation in the left subclavian vein was achieved in 96 of 100 patients, with a median capture threshold of 2.5 mA [inter-quartile range (IQR) 1.4-5.0 mA]. Stimulation of the right phrenic nerve from the subclavian vein was superior to stimulation from the SVC with lower pacing thresholds (1.8 mA IQR 1.4-3.3 vs. 6.0 mA IQR 3.4-8.0, P < 0.001). Venous pressure waveforms were obtained in all patients and attenuation of the waveform was always observed prior to onset of phrenic nerve palsy. CONCLUSION: The left phrenic nerve can be stimulated from the left subclavian vein. The subclavian veins are the optimal sites for phrenic nerve stimulation. Monitoring the femoral venous pressure waveform is a novel technique for detecting impending phrenic nerve damage.

Balloon warming time is the strongest predictor of late pulmonary vein electrical reconnection following cryoballoon ablation for atrial fibrillation.

BACKGROUND: Pulmonary vein isolation by cryoballoon ablation is an accepted method of treating atrial fibrillation. Little data exist regarding factors affecting late electrical reconnection of pulmonary veins following cryoballoon ablation. OBJECTIVE: To investigate factors determining pulmonary vein reconnection in patients undergoing repeat catheter ablation for recurrent atrial fibrillation following cryoballoon ablation. METHODS: Fifty-one consecutive patients undergoing repeat catheter ablation for recurrent atrial fibrillation following initial cryoballoon ablation underwent retrospective assessment of initial cryoablation characteristics, including balloon and vein sizes, venogram occlusion score, balloon freezing time from 0 to -30 °C, nadir temperature, and balloon warming time from -30 to +15 °C, recorded during the initial cryoballoon procedure. RESULTS: Of 199 veins assessed, 91 had reconnected (1.8 per patient). Balloon warming time (odds ratio [OR] 3.21; 95% confidence interval [CI] 2.00-5.13; P < .0001), nadir temperature (OR 1.94; 95% CI 1.42-2.66; P < .0001), vein occlusion score (OR 1.74; 95% CI 1.29-2.34; P = .0003), and balloon freezing time (OR 1.58; 95% CI 1.03-2.42; P = .037) predicted pulmonary vein reconnection. On multivariate analysis, balloon warming time (OR 3.71; 95% CI 2.2-6.24; P ≤ .0001), pulmonary vein size (OR 1.63; 95% CI 1.08-2.43; P = .020), and vein occlusion score (OR 1.48; 95% CI 1.06-2.08; P = .021) remained statistically significant independent predictors of pulmonary vein reconnection. The receiver operating characteristic for the multivariate model yielded an area under the curve of 0.82. CONCLUSIONS: Balloon warming time, vein occlusion score, and pulmonary vein size predict pulmonary vein reconnection. Balloon warming time was the most important predictive factor, and the manipulation of balloon warming may be a novel therapeutic strategy for improving outcomes of cryoballoon ablation for atrial fibrillation.

Immediate balloon deflation for prevention of persistent phrenic nerve palsy during pulmonary vein isolation by balloon cryoablation.

BACKGROUND: Persistent phrenic nerve palsy is the most frequent complication of cryoballoon ablation for atrial fibrillation and can be disabling. OBJECTIVES: To describe a technique-immediate balloon deflation (IBD)-for the prevention of persistent phrenic nerve palsy, provide data for its use, and describe in vitro simulations performed to investigate the effect of IBD on the atrium and pulmonary vein. METHODS: Cryoballoon procedures for atrial fibrillation were analyzed retrospectively (n = 130). IBD was performed in patients developing phrenic nerve dysfunction (n = 22). In vitro simulations were performed by using phantoms. RESULTS: No adverse events occurred, and all patients recovered normal phrenic nerve function before leaving the procedure room. No patient developed persistent phrenic nerve palsy. The mean cryoablation time to onset of phrenic nerve dysfunction was 144 ± 64 seconds. Transient phrenic nerve dysfunction was seen more frequently with the 23-mm balloon than with the 28-mm balloon (11 of 39 cases vs 11 of 81 cases; P = .036). Balloon rewarming was faster following IBD. The time to return to 0 and 20° C was shorter in the IBD group (6.7 vs 8.9 seconds; P = .007 and 16.7 vs 37.6 seconds; P<.0001). In vitro simulations confirmed that IBD caused more rapid tissue warming (time to 0°C, 14.0 ± 3.4 seconds vs 46.0 ± 8.1; P = .0001) and is unlikely to damage the atrium or pulmonary vein. CONCLUSIONS: IBD results in more rapid tissue rewarming, causes no adverse events, and appears to prevent persistent phrenic nerve palsy. Simulations suggest that IBD is unlikely to damage the atrium or pulmonary vein.

The effect of altering heart rate on ventricular function in patients with heart failure treated with beta-blockers.

BACKGROUND: Beta-blockers are effective for the treatment of heart failure, but their mechanism of action is unresolved. Heart rate reduction may be a central mechanism or a troublesome side effect. METHODS: A randomized, double-blind, parallel group study comparing chronic higher-rate (80 pulses per minute) with lower-rate (60 pulses per minute) pacing in pacemaker-dependent patients with symptomatic left ventricular (LV) systolic dysfunction, receiving beta-blockers. Gated radionuclide ventriculography (RNVG) was performed at baseline and after at least 9 months. The primary outcome was change in LV volumes, as a marker of beneficial reverse remodeling, from baseline to follow-up. RESULTS: Forty-nine patients were randomized. Mean age was 74 +/- 6 years and with LV ejection fraction of 26% +/- 9% at baseline. During 14 +/- 13 months of follow-up, 21 patients (43%) died and 25 (51%) completed the study protocol: 12 in the higher-rate and 13 in the lower-rate group. Mean LV end-diastolic (higher rate +20 +/- 104 mL vs lower rate -65 +/- 92 mL, P = .03) and systolic (higher rate +29 +/- 83 mL vs lower rate -60 +/- 74 mL, P = .006) volumes increased with higher-rate versus lower-rate pacing, whereas LV ejection fraction declined (higher rate -4.2% +/- 4.4% vs lower rate +2.2% +/- 5.4%, P = .002). CONCLUSION: Reversal of beta-blocker-induced bradycardia has deleterious effects on ventricular function, suggesting heart rate reduction is an important mediator of their effects. The prognosis of patients with pacemakers and heart failure is poor.

New generation 3-dimensional echocardiography for left ventricular volumetric and functional measurements: comparison with cardiac magnetic resonance.

AIMS: Non-invasive assessment of left ventricular (LV) structure and function is important in the evaluation of cardiac patients. This study was designed to test the accuracy and reproducibility of new generation 3-dimensional echocardiography (3DE) in measuring volumetric and functional LV indices as compared with current "gold standard" of non-invasive cardiac imaging, cardiac magnetic resonance (CMR). METHODS AND RESULTS: Sixty-four subjects with good acoustic windows, including 40 cardiac patients with LV ejection fraction (EF)<45%, 14 patients with EF>45% and 10 normal volunteers underwent 3DE using a commercially available Philips Sonos 7500 scanner equipped with a matrix phase-array x4 xMATRIX transducer, and CMR on a 1.5 T Signa CV/i scanner (GE Medical Systems). Volumetric assessment was performed with analytical 4D-LV-Analysis software (TomTec) for 3DE and MRI-Mass software (Medis) for CMR. We found no significant differences in LV end-diastolic volume (EDV), end-systolic volume (ESV) and EF with excellent correlations between the indices measured using 3DE and CMR (r=0.97, r=0.98, and r=0.94, respectively). Bland-Altman analysis showed bias of 7 ml for EDV, 3 ml for ESV and -1% for EF with 3DE with corresponding limits of agreement (2SD) of 28 ml, 22 ml and 10%, respectively. Intraobserver and interobserver variabilities were for EDV: 3% and 4% (3DE) vs 2% and 2% (CMR), for ESV: 3% and 6% (3DE) vs 2% and 3% (CMR), and for EF: 4% and 4% (3DE) vs 2% and 4% (CMR), respectively. CONCLUSION: New generation 3DE provides accurate and reproducible quantification of LV volumetric and functional data in subjects with good acoustic windows as compared with CMR.

N-terminal brain natriuretic peptide as a screening tool for heart failure in the pacemaker population.

AIMS: Assessment of N-terminal brain natriuretic peptide (NT-BNP) as a screening tool for heart failure in patients with a permanent pacemaker. METHODS AND RESULTS: Consecutive patients undergoing a routine permanent pacemaker assessment were enrolled. Patients underwent medical history and examination, echocardiography and blood sampling for NT-BNP. Analysis was performed on 261 patients (132 DDD, 121 VVI, eight others), mean age 73+/-12 years, range 34-99 years. Seventy two subjects (27%) had heart failure as defined by left ventricular ejection fraction (LVEF)

Cardiac resynchronization therapy: redefining the role of device therapy in heart failure.

That cardiac dyssynchrony can contribute to a decline in cardiac efficiency has been recognized in one form or another for at least 50 years. Although revascularization and beta-blockers can improve cardiac synchrony, there was little interest in or awareness of this clinical entity until the advent of specific, highly effective therapy using atriobiventricular pacing, often described as cardiac resynchronization therapy. Over the last few years, significant advances in cardiac resynchronization therapy technology and the publication of large-scale clinical trials using cardiac resynchronization therapy devices in patients with heart failure have led to the widespread use of these devices. This review will briefly describe the complex nature of cardiac dyssynchrony, what is known about its epidemiology, the effects of cardiac resynchronization therapy, appropriate patient selection, practical aspects, such as implantation and monitoring, and some still unanswered questions.

Clinical trials update and cumulative meta-analyses from the American College of Cardiology: WATCH, SCD-HeFT, DINAMIT, CASINO, INSPIRE, STRATUS-US, RIO-Lipids and cardiac resynchronisation therapy in heart failure.

This article continues a series of reports on recent research developments in the field of heart failure. Key presentations made at the American College of Cardiology meeting, held in New Orleans, Louisiana, USA in March 2004 are reported. These new data have been added to existing data in cumulative meta-analyses. The WATCH study randomised 1587 patients with heart failure and left ventricular systolic dysfunction to warfarin, aspirin or clopidogrel. The study showed no difference between the effects of these agents on mortality or myocardial infarction, but hospitalisations for heart failure were higher on aspirin (22.2%) compared to warfarin (16.1%). The SCD-HeFT study showed that ICD therapy reduced all-cause mortality at 5 years by 23% in patients with predominantly NYHA class II heart failure and left ventricular systolic dysfunction, but amiodarone was ineffective. The DINAMIT study showed that ICD therapy was not beneficial in patients with left ventricular dysfunction after a recent MI, even in those with risk factors for arrhythmic death. In CASINO, levosimendan improved survival compared with dobutamine or placebo in patients with decompensated heart failure. INSPIRE showed that SPECT imaging can be used to assess risk early after acute MI safely and accurately. Rimonabant was shown to be safe and effective in treating the combined cardiovascular risk factors of smoking and obesity. An overview of new developments in cardiac resynchronisation therapy (CRT) in heart failure is also reported.