Impact of sex-specific target dose in chronic heart failure patients with reduced ejection fraction.

AIMS: A recent study suggested that women with heart failure and heart failure reduced ejection fraction might hypothetically need lower doses of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers ( = renin-angiotensin-system inhibitors) and ß-blockers than men to achieve the best outcome. We assessed the current medical treatment of heart failure reduced ejection fraction in men and women in a large contemporary cohort and address the hypothetical impact of changing treatment levels in women. METHODS: This analysis is part of a large contemporary quality of heart failure care project which includes 5320 (64%) men and 3003 (36%) women with heart failure reduced ejection fraction. Detailed information on heart failure therapy prescription and dosage were collected. RESULTS: Women less often received renin-angiotensin-system inhibitors (79% vs 83%, p < 0.01), but more often ß-blockers (82% vs 79%, p < 0.01) than men. Differences in guideline-recommended target doses between sexes were relatively small. Implementing a hypothetical sex-specific dosing schedule (at 50% of the current recommended dose in the European Society of Cardiology guidelines in women only) would lead to significantly higher levels of women receiving appropriate dosing (ß-blocker 87% vs 54%, p < 0.01; renin-angiotensin-system inhibitor 96% vs 75%, p < 0.01). Most interestingly, the total number of women with >100% of the new hypothetical target dose would be 24% for ß-blockers and 52% for renin-angiotensin-system inhibitors, which can be considered as relatively overdosed. CONCLUSION: In this large contemporary heart failure registry, there were significant but relatively small differences in drug dose between men and women with heart failure reduced ejection fraction. Implementation of the hypothetical sex-specific target dosing schedule would lead to considerably more women adequately treated. In contrast, we identified a group of women who might have been relatively overdosed with increased risk of side-effects and intolerance.

Contemporary use of devices in chronic heart failure in the Netherlands.

AIMS: Despite previous surveys regarding device implantation rates in heart failure (HF), insight into the real-world management with devices is scarce. Therefore, we investigated device implantation rates in HF with reduced left ventricular ejection fraction (LVEF) in 34 Dutch centres. METHODS AND RESULTS: A cross-sectional outpatient registry was conducted in 6666 patients with LVEF < 50% and with information about device implantation available [74 (66-81) years of age; 64% male]. Patients were classified into conventional pacemakers (PM, n = 562), implantable cardioverter defibrillators (ICD, n = 1165), and cardiac resynchronization therapy with defibrillator function (CRT-D, n = 885) or pacemaker function only (CRT-P, n = 248), or no device (n = 3806). Centres were divided into ICD-implanting and CRT-implanting and referral centres. Overall, 17.5% had an ICD, 13.3% CRT-D, 3.7% CRT-P, and 8.4% PM. Of those with LVEF ≤ 30%, 42.5% had ICD or CRT-D therapy. A large variation in implantation rates existed between centres: 3-51% for ICD therapy, 0.3-44% for CRT-D therapy, 0-11% for CRT-P therapy, and 0-25% PM therapy. Implantation centres showed higher implantation rates of ICD, CRT-D, and CRT-P compared with referral centres [36% vs. 25% for defibrillators (ICD or CRT-D) and 17% vs. 9% for CRT devices (CRT-D or CRT-P), respectively, P < 0.001], independently of other factors. A large number of clinical factors were predictive for device usage. Among other, LVEF < 40% and male sex were independent positive predictors for ICD/CRT-D use [odds ratio (OR) = 3.33, P < 0.001; OR = 1.87, P = 0.019, respectively]. Older age was independently associated with less ICD/CRT-D (OR = 0.96 per year, P < 0.001) and more CRT-P/PM use (OR = 1.03 per year, P = 0.006). CONCLUSIONS: In this large Dutch HF registry, less than half of the patients with reduced LVEF received an ICD or CRT, even if LVEF was ≤30%, and a large variation between centres existed. Patients from implantation centres had more often ICD or CRT. More uniformity regarding guideline-based use of device therapy in clinical practice is needed.

Cardiac resynchronization improves microcirculation.

BACKGROUND: Although it is known that cardiac resynchronization therapy (CRT) in heart failure (HF) patients improves systemic circulation, its acute effects on microcirculation are as yet unknown. Therefore we investigated the sublingual microcirculatory changes in HF patients from CRT and right ventricular (RV) pacing by use of orthogonal polarization spectral (OPS) imaging. METHODS AND RESULTS: Twelve consecutive HF patients with a CRT device and 20 healthy individuals (HI) were included. Acute microcirculatory changes were assessed by functional capillary density (FCD) and capillary velocity (CV) measurement 6 months after CRT. FCD and CV were measured in HF patients sublingually after 15 minutes of programming 1 of 3 pacing modalities in random order (no pacing, RV pacing, and CRT). FCD was significantly higher in HI (11.2 +/- 2.1 cm/cm(2)) compared with HF patients with RV pacing (8.9 +/- 1.9 cm/cm(2); P = .03) and no pacing (8.3 +/- 2.4 cm/cm(2); P = .02). CRT (12.1 +/- 2.2 cm/cm(2)) significantly increased FCD in HF patients compared with RV pacing (8.9 +/- 1.9 cm/cm(2); P = .006) and no pacing (8.3 +/- 2.4 cm/cm(2); P = .008). CV was normal in all patients with or without pacing. CONCLUSIONS: CRT improves microcirculatory function as assessed by OPS imaging.

Varying the heart rate response to dynamic exercise in pacemaker-dependent subjects: effects on cardiac output and cerebral blood velocity.

Cerebral blood flow increases upon the transition from rest to moderate exercise, but becomes affected when the ability to raise CO (cardiac output) is limited. HR (heart rate) is considered to contribute significantly to the increase in CO in the early stages of dynamic exercise. The aim of the present study was to test whether manipulation of the HR response in patients dependent on permanent rate-responsive ventricular pacing contributes to the increase in CO, MCA V(mean) [mean MCA (middle cerebral artery) velocity] and work capacity during exercise. The effect of setting the pacemaker to DSS ('default' sensor setting) compared with OSS ('optimized' sensor setting) on blood pressure, CO, SV (stroke volume) and MCA V(mean) was evaluated during ergometry cycling. From rest to exercise at 75 W, the rise in HR in OSS [from 73 (65-87) to 116 (73-152) beats/min; P<0.05] compared with DSS [70 (60-76) to 97 (67-117) beats/min; P<0.05] was larger. There was an increase in SV during exercise with DSS, but not with OSS, such that, at all workloads, SVs were greater during DSS than OSS. The slope of the HR-CO relationship was larger with DSS than OSS (P<0.05). From rest to exercise, MCA V(sys) (systolic MCA velocity) increased in OSS and DSS, and MCA V(dias) (diastolic MCA velocity) was reduced with DSS. No changes were observed in MCA V(mean). Manipulation of the pacemaker setting had no effect on the maximal workload [133 (100-225) W in OSS compared with 129 (75-200) W in DSS]. The results indicate that, in pacemaker-dependent subjects with complete heart block and preserved myocardial function, enhancing the HR response to exercise neither augments CO by a proportional offset of the exercise-induced increase in SV nor improves cerebral perfusion.

Cardiac resynchronization induces favorable neurohumoral changes.

AIM: The aim of this article is to examine whether cardiac resynchronization therapy (CRT) induces improvements in the neurohumoral system. METHODS AND RESULTS: Thirteen patients with HF (left ventricular (LV) ejection fraction <35%) were included. Before and after 6 months of CRT, myocardial (123)I-metaiodobenzylguanidine ((123)I-MIBG) uptake indices, used as an index of neural norepinephrine reuptake and retention, and brain natriuretic peptide (BNP) levels, used as an index of LV end-diastolic pressure, NYHA classification and echocardiographic indices were assessed. Six months of CRT resulted in significant improvement in (1) NYHA classification and reduction in QRS width (P < 0.001), (2) decrease of LV end-diastolic diameter (P = 0.005), LV end-systolic diameter (P = 0.005), septal to lateral delay (P = 0.01) and mitral regurgitation (MR, P = 0.04), (3) delayed (123)I-MIBG heart/mediastinum ratios improved (P = 0.03) and (123)I-MIBG washout decreased (P = 0.001), and (4) BNP levels decreased (P = 0.001). CONCLUSIONS: Parallel to significant functional improvement and echocardiographic reverse remodeling and resynchronization, our data indicate that CRT induces favorable changes in the neurohumoral system.

Individual optimization of pacing sensors improves exercise capacity without influencing quality of life.

INTRODUCTION: Programmable pacemaker sensor features are frequently used in default setting. Limited data are available about the effect of sensor optimization on exercise capacity and quality of life (QOL). Influence of individual optimization of sensors on QOL and exercise tolerance was investigated in a randomized, single blind study in patients with VVIR, DDDR, or AAIR pacemakers. METHODS: Patients with > or =75% pacing were randomized to optimized sensor settings (OSS) or default sensor setting (DSS). Standardized optimization was performed using three different exercise tests. QOL questionnaires (QOL-q: Hacettepe, Karolinska, and RAND-36) were used for evaluation of the sensor optimization. One month before and after optimization, exercise capacity using chronotropic assessment exercise protocol and the three QOL-q were assessed. RESULTS: Fifty-four patients (26 male, 28 female) with a mean age of 65 +/- 16 years were enrolled in the study. In each group (OSS and DSS) 27 patients were included. One month after sensor optimization, the achieved maximal heart rate (HR) and metabolic workload (METS) were significantly higher in OSS when compared with DSS (124 +/- 28 bpm vs 108 +/- 20 bpm, P = 0.036; 7.3 +/- 4 METS vs 4.9 +/- 4 METS, P = 0.045). Highest HR and METS were achieved in patients with pacemakers with accessible sensor algorithms. In patients with automatic slope settings (33%), exercise capacity did not improve after sensor optimization. QOL did not improve in OSS compared with DSS. CONCLUSION: After 1 month of individual optimization of rate response pacemakers, exercise capacity was improved and maximum HR increased, although QOL remained unchanged. Accessible pacemaker sensor algorithms are mandatory for individual optimization.

Direct comparison of a contractility and activity pacemaker sensor during treadmill exercise testing.

There are limited data about the chronotropic capacity of the peak endocardial acceleration (PEA) sensor. This study directly compared the chronotropic function from the PEA and the activity (ACT) sensor. The study included 18 patients (age 73 +/- 7 years) with > or = 75% pacemaker-driven heart rate (HR) and a PEA sensor and 11 healthy controls (age 67 +/- 7 years) underwent a chronotropic assessment exercise protocol (CAEP) exercise test with the pacemaker patients in VVIR mode after programming the sensors in the default setting with adjustment of the upper sensor rate as an age related maximum value (220-age). The ACT sensor was externally strapped on the thorax. Achieved exercise duration for the patients and controls was, respectively, 9.2 +/- 3 vs 18.4 +/- 4 minutes (P <0.001). The maximal achieved HR with the PEA sensor was 124 +/- 25 beats/min, versus the ACT with 140 +/- 23, versus the controls with 153 +/- 26 beats/min (P <0.001 between the groups). For the PEA, ACT, and controls, the time to peak HR was, respectively, 11 +/- 3, 7 +/- 3.6, and 18 +/- 4 (P <0.001 between groups) and HR after 10 minutes recovery was, respectively, 80 +/- 20, 65 +/- 15, and 82 +/- 4 beats/min (P <0.001 between groups). The PEA sensor functions hypochonotroop during exercise programmed as a single sensor system. It is, therefore, preferable to combine the PEA sensor with an activity-based sensor in a dual sensor system. Although both groups had normal left ventricular functions, the exercise capacity of pacemaker patients is significantly lower than in the controls.