Abstract Background Heart Failure (HF) is increasing in prevalence and is a major cause of morbidity and mortality, despite advances in medical and device therapy. Autonomic imbalance, with excess ...sympathetic activation and decreased vagal tone, is an integral component of the pathophysiology of HF. Objectives INOVATE-HF was designed to assess the safety and efficacy of vagal nerve stimulation (VNS) among patients with heart failure and a reduced ejection fraction. Methods INOVATE-HF was a multinational, randomized trial involving 85 centers in patients with chronic HF, NYHA III symptoms and ejection fraction < 40%. Patients were assigned to device implantation to provide VNS (Active) or continued medical therapy (Control) in a 3:2 ratio. The primary efficacy endpoint was the composite of death from any cause or first event for worsening HF. Results There were 707 patients randomized and followed for a mean of 16 months. The primary efficacy outcome occurred in 132 of 436 patients in the VNS group, as compared with 70 of 271 in the control group (30.3% vs. 25.8%; hazard ratio, 1.14; 95% confidence interval CI, 0.86 to 1.53; P = 0.37). During the trial, the estimated annual mortality rates of 9.3% and 7.1%, respectively (p=0.19). Quality of life, New York Heart Association Class and 6 minute walking distance were favorably affected by VNS (p’s < 0.05), but left ventricular end-systolic volume index was not different (P=0.49). Conclusions VNS does not reduce the rate of death or HF events in chronic HF patients. (Clinical Trials.gov number NCT01303718)
Aims Obesity is a recognized risk factor for atrial fibrillation (AF), partly because of the association between body mass index (BMI) and atrial volume. We aimed to determine whether other factors ...relating to body size were related to AF. Methods and results Data were derived from a random population sample of 6903 men (mean age 51.5 years) who underwent a single midlife evaluation as part of the multifactor Swedish Primary Prevention Study. A total of 1253 men (18.2%) had a subsequent hospital discharge diagnosis (principal or secondary) of AF during a maximum follow-up of 34.3 years. Body surface area (BSA) at age 20 (calculated from recalled weight and measured height) was strongly related to subsequent AF (P < 0.0001), as were midlife BMI and weight gain from age 20 to midlife (P < 0.0001). In a Cox regression model which adjusted for midlife BMI, weight gain and other risk factors, hazard ratios (HR) 95% confidence intervals (CI) for AF for the second, third, and fourth quartile of BSA at age 20, compared with the lowest quartile, were 1.47 (95% CI, 1.22–1.76), 1.66 (95% CI, 1.38–2.00), and 2.22 (95% CI, 1.82–2.70) (P for trend <0.0001). Conclusion Large body size in youth, in an era when obesity was rare, as well as weight gain from age 20 to midlife, were both independently related to the development of AF. Given the current trends not only for obesity but also for height, a substantial increase in the incidence of AF is likely.
Implantable cardioverter-defibrillators (ICDs) have changed the way in which patients with chronic ventricular dysfunction are evaluated and treated.
To examine patient-physician communication at the ...time the decision is made to implant an ICD.
Forty-one patients with ICDs and 11 cardiologists were recruited by a national marketing research company for a study comprising patient focus groups and standardized patient interviews in 3 different metropolitan areas.
Eight patient focus groups and (separately) 22 standardized patient interviews with cardiologists.
Patient focus group findings and the results of standardized patient interviews (each cardiologist interviewed 2 patients).
The mean (SD) patient age was 61.4 (14.7) years; 21 were female. Thirty-three patients could not recall a discussion about periprocedural or long-term complications. On a scale of 1 to 10, the mean (SD) rating of the degree to which patients felt informed before the implant procedure was 5.7 (3.2) (1 indicates "not at all informed," and 10 indicates "I had all the information I needed or wanted"). The mean (SD) estimated number of patients out of 100 who would be saved by the ICD was 87.9 (20.1). A negative perception on body image and lifestyle was prevalent. Across 22 standardized patient interviews, cardiologists frequently (in >17 of 22 of interviews) did not address or minimized or denied quality-of-life issues and long-term consequences of ICD placement, including the risk for depression, anxiety, and inappropriate delivery of shock or device advisory. In 15 of 22 of the standardized patient interviews, cardiologists used unexplained medical terms or jargon.
Patient-physician communication about ICDs is characterized by unclear representation and omission of information to patients, with notable lack of attention to psychological and long-term risks. Training of cardiologists on information exchange with patients may promote informed decision making and preempt threats to patient quality of life.
Imbalance between the parasympathetic and sympathetic nervous systems is a recognized contributor to progression of chronic heart failure. Current therapy with beta adrenergic antagonists is designed ...to moderate the up-regulation of norepinephrine and sympathetic effects; however, to date, there are no therapies that specifically address the withdrawal of parasympathetic influences on cardiac function and structure.
In order to evaluate the impact of vagus nerve stimulation, an international multi-center randomized clinical trial (INOVATE-HF) has been designed to assess safety and efficacy of vagus nerve stimulation in symptomatic patients with heart failure on optimal medical therapy using the CardioFit System (BioControl Medical, Yehud, Israel). Up to 650 patients from 80 sites will be recruited and randomized in a 3:2 ratio to receive active treatment or standard optimal medical therapy. Inclusion criteria include left ventricular systolic dysfunction, the presence of New York Heart Association Class III symptoms, sinus rhythm, and QRS width less than 120 milliseconds. The study is powered to detect differences in the primary efficacy end point of all-cause mortality and heart failure hospitalization and 2 safety end points.
Vagal nerve stimulation with CardioFit as a treatment for symptomatic heart failure is under active investigation as a novel approach to restore balance between the sympathetic and parasympathetic nervous systems. If shown to be safe and effective in decreasing heart failure events and mortality, this novel approach will impact the treatment paradigm for heart failure.
Abstract Background Patients with decompensated heart failure, volume overload, and hyponatremia are challenging to manage. Relatively little has been documented regarding the clinical course of ...these patients during standard in-hospital management or with vasopressin antagonism. Methods and Results The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan database was examined to assess the short-term clinical course of patients hospitalized with heart failure and hyponatremia and the effect of tolvaptan on outcomes. In the placebo group, patients with hyponatremia (serum Na+ <135mEq/L; n = 232), compared with those with normonatremia at baseline (n = 1785), had less relief of dyspnea despite receiving higher doses of diuretics (59.2% vs 69.2% improved; P < .01) and worse long-term outcomes. In the hyponatremia subgroup from the entire trial cohort (n = 475), tolvaptan was associated with greater likelihood of normalization of serum sodium than placebo (58% vs 20% and 64% vs 29% for day 1 and discharge, respectively; P < .001 for both comparisons), greater weight reduction at day 1 and discharge (0.7 kg and 0.8 kg differences, respectively; P < .001 and P = .008), and greater relief of dyspnea ( P = .03). Among all hyponatremic patients, there was no effect of tolvaptan on long-term outcomes compared with placebo. In patients with pronounced hyponatremia (<130 mEq/L; n = 92), tolvaptan was associated with reduced cardiovascular morbidity and mortality after discharge ( P = .04). Conclusions In patients with decompensated heart failure and hyponatremia, standard therapy is associated with less weight loss and dyspnea relief, and unfavorable longer-term outcomes compared to those with normonatremia. Tolvaptan is associated with more favorable in-hospital effects and, possibly, long-term outcomes in patients with severe hyponatremia.
Background Prior research suggests an association between clinical outcomes in heart failure (HF) and social determinants of health (SDoH). Because providers should identify and address SDoH in care ...delivery, we evaluated how SDoH have been defined, measured, and evaluated in studies that examine HF outcomes. Methods and Results Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, databases were searched for observational or interventional studies published between 2009 and 2021 that assessed the influence of SDoH on outcomes. Selected articles were assessed for quality using a validated rating scheme. We identified 1373 unique articles for screening; 104 were selected for full-text review, and 59 met the inclusion criteria, including retrospective and prospective cohort, cross-sectional, and intervention studies. The majority examined readmissions and hospitalizations (k=33), mortality or survival (k=29), and success of medical devices and transplantation (k=8). SDoH examined most commonly included race, ethnicity, age, sex, socioeconomic status, and education or health literacy. Studies used a range of 1 to 9 SDoH as primary independent variables and 0 to 7 SDoH as controls. Multiple data sources were employed and frequently were electronic medical records linked with national surveys and disease registries. The effects of SDoH on HF outcomes were inconsistent because of the heterogeneity of data sources and SDoH constructs. Conclusions Our systematic review reveals shortcomings in measurement and deployment of SDoH variables in HF care. Validated measures need to be prospectively and intentionally collected to facilitate appropriate analysis, reporting, and replication of data across studies and inform the design of appropriate, evidence-based interventions that can ameliorate significant HF morbidity and societal costs.
Digitalis Hauptman, P J; Kelly, R A
Circulation (New York, N.Y.),
03/1999, Letnik:
99, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Cardiac glycosides have played a prominent role in the therapy of congestive heart failure since William Withering codified their use in his late 18th century monograph on the efficacy of the leaves ...of the common foxglove plant (Digitalis purpurea). Despite their widespread acceptance into medical practice in the ensuing 200 years, both the efficacy and the safety of this class of drugs continue to be a topic of debate. Moreover, despite the fact that the molecular target for the cardiac glycosides, the alpha-subunit of sarcolemmal Na+K+-ATPase (or sodium pump) found on most eukaryotic cell membranes, has been known for several decades, it remains controversial whether the sympatholytic or positive inotropic effects of these agents is the mechanism most relevant to relief of heart failure symptoms in humans with systolic ventricular dysfunction. Herein, we review the molecular and clinical pharmacology of this venerable class of drugs, as well as the manifestations of digitalis toxicity and their treatment. We also review in some detail recent clinical trials designed to examine the efficacy of these drugs in heart failure, with a focus on the Digoxin Investigation Group data set. Although, in our opinion, the data on balance warrant the continued use of these drugs for the treatment of symptoms of heart failure in patients already receiving contemporary multidrug therapy for this disease, the use of digitalis preparations will inevitably decline with the maturation of newer pharmacotherapies.
Abstract Depression is a common comorbidity associated with epilepsy. However, the etiology of depression is difficult to establish given the heterogeneity in both epilepsy and depression. ...Nevertheless, the co-occurrence is so common that a bidirectional relationship between depression and epilepsy has been theorized. Persons with temporal lobe seizure foci and partial-onset epilepsy may be more vulnerable to the development of depression. In pediatrics, depression differs but may be readily identified by understanding nuances of mood states and variability of neurovegetative symptom presentation. Although no clear treatment guidance exists in the context of epilepsy, antidepressants have been relatively well studied in pediatrics and are effective and well tolerated. Anticonvulsant drugs may also improve depressive symptoms though clinical research is lacking in pediatrics. Treatment of depression may independently improve outcome for epilepsy and for quality of life. Future studies will clarify etiologies of depression in the context of epilepsy and improve the evidence base for treatment outcomes.
Oral malignant melanoma (OMM) in the dog is often locally aggressive with a high metastatic potential and there are few treatment options that have been demonstrated to improve outcome of this ...disease. The purpose of this study was to determine whether adjunctive treatment with the Oncept melanoma vaccine affected the outcome of dogs with OMM that had achieved loco‐regional cancer control. Medical records from 45 dogs that presented to the Animal Cancer and Imaging Center were reviewed, including 30 dogs with stage II and III disease. Dogs that received the vaccine did not achieve a greater progression‐free survival, disease‐free interval or median survival time than dogs that did not receive the vaccine.
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