Detrimental Immediate- and Medium-Term Clinical Effects of Right Ventricular Pacing in Patients With Myocardial Fibrosis.

BACKGROUND: Long-term right ventricular (RV) pacing leads to heart failure or a decline in left ventricular (LV) function in up to a fifth of patients. We aimed to establish whether patients with focal fibrosis detected on late gadolinium enhancement cardiovascular magnetic resonance (CMR) have deterioration in LV function after RV pacing. METHODS: We recruited 84 patients with LV ejection fraction ≥40% into 2 observational CMR studies. Patients (n=34) with a dual-chamber device and preserved atrioventricular conduction underwent CMR in 2 asynchronous pacing modes (atrial asynchronous and dual-chamber asynchronous) to compare intrinsic atrioventricular conduction with forced RV pacing. Patients (n=50) with high-grade atrioventricular block underwent CMR before and 6 months after pacemaker implantation to investigate the medium-term effects of RV pacing. RESULTS: The key findings were (1) initiation of RV pacing in patients with fibrosis, compared with those without, was associated with greater immediate changes in both LV end-systolic volume index (5.3±3.5 versus 2.1±2.4 mL/m2; P<0.01) and LV ejection fraction (-5.7±3.4% versus -3.2±2.6%; P=0.02); (2) medium-term RV pacing in patients with fibrosis, compared with those without, was associated with greater changes in LV end-systolic volume index (8.0±10.4 versus -0.6±7.3 mL/m2; P=0.008) and LV ejection fraction (-12.3±7.9% versus -6.7±6.2%; P=0.012); (3) patients with fibrosis did not experience an improvement in quality of life, biomarkers, or functional class after pacemaker implantation; (4) after 6 months of RV pacing, 10 of 50 (20%) patients developed LV ejection fraction <35% and were eligible for upgrade to cardiac resynchronization according to current guidelines. All 10 patients had fibrosis on their preimplant baseline scan and were identified by >1.1 g of fibrosis with 90% sensitivity and 70% specificity. CONCLUSIONS: Fibrosis detected on CMR is associated with immediate- and medium-term deterioration in LV function following RV pacing and could be used to identify those at risk of heart failure before pacemaker implantation.

Chest pain following permanent pacemaker insertion a case of pneumopericardium due to atrial lead perforation.

Permanent pacemaker (PPM) implantation is an increasingly common procedure with complication rate estimated between 3% and 6%. Cardiac perforation by pacemaker lead(s) is rare, but a previous study has shown that it is probably an underdiagnosed complication. We are presenting a case of a patient who presented 5 days after PPM insertion with new-onset pleuritic chest pain. She had a normal chest X-ray (CXR), and acceptable pacing checks. However, a CT scan of the chest showed pneumopericardium and pneumothorax secondary to atrial lead perforation. The pain only settled by replacing the atrial lead. A repeat chest CT scan a few months later showed complete resolution of the pneumopericardium and pneumothorax. We believe that cardiac perforation can be easily missed if associated with normal CXR and acceptable pacing parameters. Unexplained chest pain following PPM insertion might be the only clue for such complication, although it might not always be present.

Promoting Self-Management of Hypertension in the African-American Church.

Hypertension (HTN) continues to be one of the most preventable diseases that have global impact. The prevalence of HTN in African-Americans is considered to be among the highest in the world. This investigation sought to determine whether a church-based self-management program would aid African-American adults (18 years of age and above) in reducing their blood pressure (BP). The theoretical foundation was the Health Belief Model. The clinical question was: Will a church-based American Heart Association (AHA) program on BP self-management decrease BP in African-American adults (aged 18 and above) who belong to a local Christian church? The quantitative methodology and pretest-posttest single group design were used in this investigation. The sample was a convenience sampling of 23 Christian church members. The participants enrolled in the AHA's "Check. Change. Control®. Tracker." There were only two demographic variables that were significant at the 0.05 level (2-tailed) with the initial BP: age was 0.585 (p = 0.05) and having children was -0.434 (p = 0.039). The paired t-test was computed for the initial and final systolic BPs. The paired t-test for these variables was 1.844 (p = 0.079). The paired t-test was computed for the initial and final diastolic BPs. The paired t-test for these variables was 1.724 (p = 0.079). These results indicated there were no improvements after the intervention. However, data supported clinical significance.

Do Alarm Devices Reduce Falls in the Elderly Population?

It is plausible to assume that healthcare practitioners do not know to what extent bed/body alarms could reduce falls when compared to other fall prevention measures. Thus, the purpose of this study was to determine the following: Do bed/body alarms reduce the incidence of falls and/or subsequent injuries in a facility that uses such devices, as compared to a facility in which no bed/body alarms were used among the elderly over a 5-month period? A retrospective chart review was conducted in 2 homogenous long-term care facilities. The sample size was N = 160 across the 2 facilities and included 80 residents at each facility. Analysis of the data indicated that there was a total of 94 falls in the facility that used the bed/body alarms, and a total of 70 falls in the facility that did not use the bed/body alarms. Further analysis of the data indicated that there was a slightly higher mean for falls with injuries within the facility that did use the bed/body alarms (M = 18.800) as compared to a mean of 14.0 for the facility that did not use the bed/body alarms (p = .001). The analysis of data suggested that the use of bed/body alarms did not reduce falls within the elderly population. However, since response time to the alarms was not noted, it is plausible to assume that reduction in falls could have been achieved if response time was also studied as an intervening variable.

Alerts for Nurse Practitioners: Caring for Pregnant Women with Zika Virus.

There have been 3,625 cases of Zika virus in the United States and 22,069 cases in the U.S. Territories (Centers for Disease Control and Prevention [CDC], 2016a). As a result, Zika virus is rapidly becoming a major health problem in certain areas of the United States. The CDC is reporting valuable data and clinical recommendations almost every month. With this rapid dissemination of information, it is difficult for most health-care providers to keep up. Therefore, this article was written to provide health-care providers with the most current information (as of September, 2016)for managing patients with Zika virus.

Transient right-to-left intracardiac shunt following a right ventricular myocardial infarction.

A 56-year-old smoker presented with a 3-day history of intermittent chest pain. Cardiovascular examination on admission was normal. ECG showed minimal (<1 mm) ST elevation in lead III, and right-sided leads revealed similar mild ST-elevation. Troponin I was elevated at 10.91. He was managed as a delayed-presentation ST-elevation myocardial infarction case. 12 h following admission, he developed oxygen-resistant hypoxia and hypotension. There were no clinical or radiological signs of pulmonary congestion. CT pulmonary angiogram revealed no pulmonary embolus. A bubble-contrast echocardiogram confirmed an active interatrial right-to-left shunt without Valsalva provocation. His hypoxia steadily improved over the following 24 h and he did not require any shunt closure. A repeat bubble contrast echocardiogram showed that the shunt was now only active following a Valsalva manoeuvre. Transoesophageal echocardiography confirmed a patent foramen ovale. This is a rare but important cause of resistant hypoxia following a right-heart infarct.

Polymorphisms of adrenoceptors are not associated with an increased risk of adverse event in heart failure: a MERIT-HF substudy.

BACKGROUND: Enhanced sympathetic activation has a central role in the development of heart failure (HF). We assessed whether the alpha(2C)-adrenoceptor (Del322-325) polymorphism exclusively or in combination with a beta(1)-adrenoceptor (Arg389) polymorphism, each with known independent effects on sympathetic function, were associated with an increased risk of adverse events in HF. METHODS AND RESULTS: A total of 526 patients enrolled in the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure study were genotyped for both adrenoceptor polymorphisms. The distribution of alpha(2C) genotypes was similar between the event and nonevent groups. However, a reduced prevalence of the Del322-325 allele was found in individuals with ischemic congestive HF (P=.022). Patients possessing both the alpha(2C) Del322-325 and beta(1) Arg389 alleles had no increased risk of events. Adjusting for confounding variables and the beta(1) Arg389Gly polymorphism, the odds ratio of being ins/del + del/del for the alpha(2C) Del322-325 and having an event was 0.89 with 95% CI 0.49-1.63, P=.715. Similarly, adjusting for confounding variables and the alpha(2C) Del322-325 polymorphism the odds ratio of being Arg/Arg or Arg/Gly for the beta(1) Arg389Gly polymorphism and having an event was 1.13 with 95% CI 0.52-2.17, P=.864. CONCLUSIONS: The alpha(2C) Del322-325 polymorphism exclusively or in combination with the beta(1)Arg389 allele is not associated with an increased risk of adverse events in HF.

The VEGF +405 CC promoter polymorphism is associated with an impaired prognosis in patients with chronic heart failure: a MERIT-HF substudy.

BACKGROUND: A common polymorphism positioned at +405 of the vascular endothelial growth factor (VEGF) gene is known to influence VEGF protein production. In contrast, a second polymorphism, positioned at -460 polymorphism, has no reported functional effects. VEGF is linked to angiogenesis and might directly influence the clinical outcome of patients with chronic heart failure (CHF). We investigated the association between two VEGF polymorphisms and morbidity and mortality in patients with CHF. METHODS AND RESULTS: VEGF promoter polymorphisms +405 and -460 were examined in 596 CHF patients enrolled in the Metoprolol CR/XL Randomized Intervention Trial in Heart Failure (MERIT-HF) study and in 187 healthy controls. In CHF patients, a risk ratio for each genotype was calculated using the combined endpoint of all-cause mortality or hospitalization. The allele frequencies of the +405 and -460 polymorphisms for the CHF cohort and for 187 healthy controls were not significantly different. However, the presence of the +405 CC genotype (frequency 0.14) was independently associated with an adverse outcome as described by the MERIT study combined endpoint compared with the +405 GG genotype (risk ratio 1.65; 95%CI 1.03-2.64; P = .039). The -460 polymorphism was not associated with an altered prognosis ( P = .60). CONCLUSION: Our results indicate that the VEGF +405 CC genotype is associated with an adverse clinical outcome in patients with CHF. This genotype has been associated with lower plasma VEGF levels, suggesting a possible mechanism of action for the gene variant. This belief is further supported by the fact that the VEGF -460 polymorphism, which does not affect plasma VEGF levels, did not adversely affect the prognosis.

An evaluation of the beta-1 adrenergic receptor Arg389Gly polymorphism in individuals with heart failure: a MERIT-HF sub-study.

BACKGROUND: The Glycine389 variant of the beta-1 adrenergic receptor (beta1AR) generates markedly less cAMP when stimulated in vitro than the more prevalent Arginine389 variant. AIMS: The aim of this MERIT-HF sub-study was to ascertain whether this Glycine389 variant favourably influences outcome in heart failure similar to that observed with beta-blockers. METHODS: We identified the genotype at amino acid 389 of the beta1AR in 600 patients enrolled in the MERIT-HF study (UK and Dutch participants). A risk-ratio (RR) for each genotype was calculated using the combined endpoint of all cause mortality or hospitalisation (time to first event). A pharmacogenetic effect of this polymorphism was also sought by evaluating the effect of Metoprolol CR/XL on heart rate amongst the three genotypes. RESULTS: The prevalence of the three genotypes was ArgArg 51.3%, ArgGly 40.2%, GlyGly 8.5%. The presence of the Gly allele was not associated with a significant benefit on the combined endpoint, RR=0.94; confidence intervals (CI), 0.69-1.29 (P=0.72). This is in contrast to the highly significant benefit of Metoprolol CR/XL observed in this sub-study population, RR=0.60; CI, 0.44-0.83 (P=0.002). No effect of the polymorphism was observed on the magnitude of heart rate reduction attained by Metoprolol CR/XL. CONCLUSION: In contrast to the benefits of beta-1 selective blockade, we have demonstrated that the Gly389 allele does not confer a significant mortality/morbidity benefit in heart failure patients. We have found no evidence of a pharmacogenetic effect of this biochemically functional polymorphism.

Chronic beta2-adrenergic receptor stimulation increases proliferation of human cardiac fibroblasts via an autocrine mechanism.

OBJECTIVE: The aim of this study was to determine whether chronic beta-adrenergic receptor (beta-AR) stimulation induces proliferation of human cardiac fibroblasts and to investigate the mechanism(s) involved. METHODS AND RESULTS: In vitro cultures of human cardiac fibroblasts were established from biopsies of right atrial appendage. RT-PCR analysis and pharmacological studies demonstrated that these cells express predominantly the beta(2)-AR subtype coupled to activation of adenylyl cyclase and p44/42 mitogen-activated protein kinase (MAPK). Proliferation was determined by cell counting over a 6-day period in medium containing 2.5% fetal calf serum (control) or supplemented with the non-selective beta-AR agonist isoproterenol (ISO). ISO induced a concentration-dependent increase in cardiac fibroblast proliferation, which was maximal at 1 micromol/l. This increased proliferation was inhibited by the beta(2)-AR-selective antagonist ICI-118,551, but not the beta(1)-AR-selective antagonist atenolol. Direct activation of adenylyl cyclase alone (0.1-10 micromol/l forskolin) stimulated cyclic AMP production and MAPK activation, but did not induce cell proliferation. Since catecholamines are not considered to be 'classical' growth factors, we subsequently investigated whether beta(2)-AR stimulation results in secretion of growth factors that are able to stimulate proliferation in an autocrine manner. Conditioned medium obtained from cardiac fibroblasts treated with ISO for 48 h increased proliferation of parallel cultures of fibroblasts in the presence of the beta-AR antagonist alprenolol. Heat-treatment of this conditioned medium fully prevented the increase in cell proliferation, indicating that the autocrine factor(s) are heat-sensitive proteins. CONCLUSIONS: Chronic beta(2)-AR stimulation increases proliferation of human cardiac fibroblasts via a mechanism involving increased secretion of heat-sensitive growth factors.