Does a Gender Difference in Response to Cardiac Resynchronization Therapy Exist?

BACKGROUND: Cardiac resynchronization therapy (CRT) has a beneficial effect on clinical symptoms, exercise capacity, and systolic left ventricular (LV) performance in patients with heart failure. The aim of the current study was to evaluate whether a gender difference exists in response to CRT. METHODS: Consecutive patients with end-stage heart failure (New York Heart Association, NYHA, class III-IV), LV ejection fraction (LVEF) < or =35%, QRS duration >120 ms, and left bundle branch block configuration underwent CRT. At baseline and 6 months post-CRT, clinical and echocardiographic parameters were evaluated; follow-up was obtained up to 5 years. The effects of CRT were compared between women and men. RESULTS: The study population comprised 137 men and 36 women (mean age 66 +/- 11 years). No differences in baseline characteristics were observed except that nonischemic cardiomyopathy was more frequent in women than men (67% vs 38%, P < 0.05). In all patients, clinical and echocardiographic parameters improved significantly at 6-month follow-up. The magnitude of improvement in different parameters was similar between women and men, e.g., the improvement in NYHA Class was 0.9 +/- 0.6 in women and 1.0 +/- 0.7 in men (NS) and the increase in LVEF was 8 +/- 8% in women as compared to 7 +/- 9% in men (NS). The percentage of individual responders was not different between women and men (76% vs 80%, NS) and 2-year survival was comparable for women and men (84% vs 80%, NS). CONCLUSION: No gender differences were observed in response to CRT and long-term survival after CRT.     

Does Disseminated Intravascular Coagulation Lead to Multiple Organ Failure?

Microvascular dysfunction with its associated impaired regional oxygen transport and use is believed to be the final common pathway in the development of multiple organ failure. The precise mechanisms underlying this dysfunction, however, are uncertain. Activation of the coagulation system is a key feature in the pathogenesis of sepsis, but whether it is also the cause of multiple organ failure is unclear. This article discusses the evidence for and against a key role for disseminated intravascular coagulation in the pathogenesis of multiple organ failure.     

Is There a Role for Ivabradine in the Contemporary Management of Patients with Chronic Heart Failure in Academic and Community Heart Failure Clinics in Canada?

Introduction

In patients with heart failure (HF) and reduced ejection fraction, increased heart rate (HR) is an independent risk factor for adverse outcomes. In systolic HF treatment with the If inhibitor ivabradine trial (SHIFT), Ivabradine improved survival when added to conventional treatment including β-blockers. However, the extent of benefit in the real world is unclear. We examined the characteristics of patients on guideline-directed therapy and determined who had SHIFT-like characteristics.

Methods

A total of 1096 patients with chronic HF were reviewed from June 2014 to April 2015 in two HF clinics in Toronto: an academic institution (AI), and a community hospital (CH) clinic. SHIFT-like characteristics [left ventricular ejection fraction (LVEF) ≤35%; sinus rhythm; and HR ≥ 70 bpm] were described.

Results

For all patients, mean age was 75 ± 13 years, overall LVEF was 44 ± 15%, AI less than CH (41.9 ± 14.0% vs. 45.7 ± 15.0%; p < 0.0001). More than two-thirds of patients in both groups were on β-blockers; with less than one-third at target dose. The proportion of patients with SHIFT-like characteristics was 8.4% AI and 11.7% CH, respectively (p = 0.0658).

Conclusion

In HF clinics from both academic and community hospitals in Toronto, up-titration in the dose of β-blockers and other guideline therapy can be improved on. A small proportion of patients with HF and SHIFT-like characteristics may potentially benefit from the addition of Ivabradine, just approved in Canada; this number will be further reduced if target dosage for β-blockers is achieved.

Funding

Servier Inc.

     

Does Early Goal-Directed Therapy Decrease Mortality Compared with Standard Care in Patients with Septic Shock?

Background

Current international guidelines for the treatment of patients with severe sepsis and septic shock recommend that patients receive targeted care to various physiologic endpoints, thereby optimizing tissue perfusion and oxygenation. These recommendations are primarily derived from a protocol published >15 years ago, which was viewed by many as complex and was therefore not widely adopted. Instead, many emergency physicians focused on the administration of early antibiotics, source control, aggressive fluid resuscitation, vasoactive medications as needed to maintain mean arterial blood pressure, and careful monitoring of these patients. The primary goal of this literature search was to determine if there is a mortality benefit to the early goal-directed protocol recommended by current international sepsis guidelines compared to current usual care.

Should Acute Treatment with Inhaled Beta Agonists be Withheld from Patients with Dyspnea Who May Have Heart Failure?

In patients with dyspnea, prehospital and emergency providers make therapeutic decisions before a diagnosis is established. Inhaled beta-2 agonists are frontline treatment for patients with dyspnea due to asthma or chronic obstructive pulmonary disease (COPD) exacerbations. However, these agents have been associated with increased adverse events when administered chronically to heart failure patients. Our goal was to determine the safety and efficacy of acute administration of inhaled beta-2 agonists to patients with heart failure. MEDLINE and EMBASE searches were performed using the terms "beta agonists," "albuterol," "congestive heart failure," and "pulmonary edema." Bibliographies of relevant articles were searched. Only studies addressing acute effects of beta-2 agonists were included for analysis. Twenty-four studies comprising 434 patients were identified that addressed the acute delivery of beta-2 agonists in subjects with heart failure--five studies with inhaled administration and 19 with systemic administration. No study directly evaluated the effects of inhaled beta-2 agonists to patients with acutely decompensated heart failure. Treatment of heart failure patients with beta-2 agonists resulted in transient improvements in pulmonary function and cardiovascular hemodynamics. Only one investigation reported an association between beta-2 agonist use and an increase in malignant dysrhythmias. Investigations in animal models of heart failure and acute lung injury demonstrated resolution of pulmonary edema with beta agonist administration. There is insufficient evidence to suggest that acute treatment with inhaled beta-2 agonists should be avoided in patients with dyspnea who may have heart failure. Based on small studies and indirect evidence, administration of beta-2 agonists to patients with heart failure seems to improve pulmonary function, cardiovascular hemodynamics, and resorption of pulmonary edema. Although an increase in adverse effects with the use of beta-2 agonists cannot be ruled out based on these data, there was no evidence of an increase in clinically significant dysrhythmias, especially when administered by inhalation. Based on these findings, further study should focus on the clinical outcomes of patients with acutely decompensated heart failure who are treated with inhaled beta-2 agonist therapy.     

Can Virtual Reality-Assisted Therapy Offer Additional Benefits to Patients With Vestibular Disorders Compared With Conventional Vestibular Physical Therapy? A Meta-analysis

ObjectiveTo determine whether virtual reality-assisted therapy (VRAT) significantly improves the treatment of peripheral or central vestibular disorders when compared with conventional vestibular physical therapy (CVPT) alone. Indicators of vestibular symptoms are used to determine this.Data SourcesTwo reviewers independently searched PubMed, EMBASE, ClinicalTrials.gov, Web of Science, and the Cochrane Collaboration database from January 2010 to January 2022 for studies reporting on VRAT in vestibular disorders.Study SelectionRandomized controlled trials (RCTs) were included that mainly focused on the following measures: the Dizziness Handicap Inventory (DHI), Simulator Sickness Questionnaire, visual analog scale, and balance measures such as the Activities-specific Balance Confidence Scale (ABC), timed Up and Go test, sensory organization test, and center of pressure. The primary outcome was assessment of symptomatic changes before and after VRAT.Data ExtractionTwo authors independently conducted the literature search and selection. After screening, meta-analysis was performed on the RCTs using RevMan 5.3 software.Data SynthesisThe results showed that VRAT produced significantly greater improvement than CVPT alone in scores of DHI-Total (standardized mean difference [SMD]: -7.09, 95% confidence interval [CI]: [-12.17, -2.00], P=.006), DHI-Functional (SMD=-3.66, 95% CI: [-6.34, -0.98], P=.007), DHI-Physical (SMD=-3.14, 95% CI: [-5.46, -0.83], P=.008), and DHI-Emotional (SMD=-3.10, 95% CI: [-5.13, -1.08], P=.003). ABC scores did not show improvement (SMD: 0.58, 95% CI: [-3.69, 4.85], P=.79). Subgroup analysis showed that DHI-Total between-group differences were insignificant for central vestibular disorders (SMD=-1.47, 95% CI: [-8.71, -5.78], P=.69), although peripheral disorders showed significant improvements (SMD=-9.58, 95% CI: [-13.92, -5.25], P<.0001). However, the included studies showed high heterogeneity (I²>75%).ConclusionsVRAT may offer additional benefits for rehabilitation from vestibular diseases, especially peripheral disorders, when compared with CVPT alone. However, because of high heterogeneity and limited data, additional studies with a larger sample size and more sensitive and specific measurements are required to conclusively determine the evidence-based utility of virtual reality.     

Should Benzodiazepines be Used for Reducing Dyspnea in Patients with Advanced Illnesses?

Dyspnea is a common and highly distressing symptom in patients with advanced illnesses. Many patients continue to experience chronic dyspnea despite optimal management of underlying disease(s) and various non-pharmacologic interventions, necessitating the consideration of pharmacologic therapies for palliation of dyspnea. One commonly asked question by clinicians is whether benzodiazepines have a role in the palliation of dyspnea. In this “Controversies in Palliative Care” article, three groups of thought leaders independently answer this question. Specifically, each group provides a synopsis of the key studies that inform their thought processes, share practical advice on their clinical approach, and highlight the opportunities for future research. All three groups suggest that benzodiazepines alone do not confer a benefit for dyspnea in advanced illnesses based on existing data. They also expressed concerns about the potential adverse effects such as delirium and drowsiness and recommended against benzodiazepines as first line pharmacologic therapy. Some groups suggest that benzodiazepines may be used in highly selected patients with severe anxiety associated with dyspnea. Some investigators may also consider the adjunctive use of benzodiazepines in patients with severe dyspnea despite opioids, particularly if life expectancy is limited. Benzodiazepines also have a role in palliative sedation for refractory dyspnea in the last days of life. More research is needed to confirm the benefit of benzodiazepines in these populations.     

Ca2+‐Binding Proteins in Dogs with Heart Failure: Effects of Cardiac Contractility Modulation Electrical Signals

Background: In dogs with heart failure (HF), chronic therapy with cardiac contractility modulation (CCM) electrical signals delivered to left ventricular (LV) muscle during the absolute refractory period improves LV function. This study examined the effects of CCM therapy on the expression of calcium (Ca²⁺)‐binding proteins (CBPs) in dogs with HF. Methods and Results: Studies were performed in LV tissue from seven CCM‐treated HF dogs, seven untreated HF dogs, and six normal (NL) dogs. mRNA expression of S100A1, sorcin, presenillin‐1 (PS1), PS2, histidine‐rich Ca²⁺‐binding protein (HRC), and 18S ribosomal RNA (18S), a housekeeping gene, was measured using RT‐PCR. Protein levels of CBPs and calsequestrin (CSQ) were determined by Western blotting. No difference was observed in the expression of 18S and CSQ among study groups. Compared with NL, the expression of S100A1, sorcin, and HRC was decreased, whereas the expression of PS2 was increased in untreated HF dogs. CCM therapy normalized the expression of S100A1, sorcin, and PS2 but not of HRC. No change was seen in the expression of PS1 among study groups. Conclusion: CCM therapy restores LV expression of S100A1, PS2, and sorcin. Normalization of CBPs may partly contribute to improved LV function in HF following CCM therapy.     

Can Homeopathy Bring Additional Benefits to Thalassemic Patients on Hydroxyurea Therapy? Encouraging Results of a Preliminary Study

Several homeopathic remedies, namely, Pulsatilla Nigricans (30th potency), Ceanothus Americanus (both mother tincture and 6th potency) and Ferrum Metallicum (30th potency) selected as per similia principles were administered to 38 thalassemic patients receiving Hydroxyurea (HU) therapy for a varying period of time. Levels of serum ferritin (SF), fetal hemoglobin (HbF), hemoglobin (Hb), platelet count (PC), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH), white blood cell (WBC) count, bilirubin content, alanine amino transferase (ALT), aspartate amino transferase (AST) and serum total protein content of patients were determined before and 3 months after administration of the homeopathic remedies in combination with HU to evaluate additional benefits, if any, derived by the homeopathic remedies, by comparing the data with those of 38 subjects receiving only HU therapy. Preliminary results indicated that there was a significant decrease in the SF and increase in HbF levels in the combined, treated subjects. Although the changes in other parameters were not so significant, there was a significant decrease in size of spleen in most patients with spleenomegaly and improvement in general health conditions along with an increased gap between transfusions in most patients receiving the combined homeopathic treatment. The homeopathic remedies being inexpensive and without any known side-effects seem to have great potentials in bringing additional benefits to thalassemic patients; particularly in the developing world where blood transfusions suffer from inadequate screening and fall short of the stringent safety standards followed in the developed countries. Further independent studies are encouraged.