Aims
Many patients with heart failure and reduced EF remain at high risk for hospitalization despite evidence‐based therapy. Digoxin may decrease hospitalization; however, uncertainty persists ...concerning its proper administration and effect on mortality. This study investigated whether using dose response concepts to re‐evaluate the relationship between serum digoxin concentration and key mortality outcomes in patients with reduced EF in the Digitalis Investigation Group trial would help clarify efficacy and safety.
Methods and results
Multivariable Cox proportional hazards modelling and propensity score adjustment assessed the relationship between serum digoxin concentration (≥0.5 ng/mL) as a continuous variable and mortality outcomes. In patients treated with digoxin, a significant linear association was found between serum concentration and all‐cause mortality adjusted hazard ratio (HR) 1.25, 95% confidence interval (CI) 1.14–1.38, P < 0.001 per 0.5 ng/mL increase in serum concentration. Based on this relationship, a bidirectional association was found between digoxin therapy and all‐cause mortality when compared with placebo. The lowest serum concentrations (0.5–0.7 ng/mL) were associated with the lowest risk of all‐cause mortality (adjusted HR 0.77, 95% CI 0.67–0.89, P < 0.001) while high serum concentrations (1.6–2.0 ng/mL) were associated with increased mortality (adjusted HR 1.33, 95% CI 1.12–1.58, P = 0.001). Consistent with this finding, lower serum concentrations (0.5–0.7 ng/mL) were associated with reduced death from worsening heart failure and a neutral effect on cardiovascular death not due to worsening heart failure.
Conclusion
These findings favour targeting serum concentrations from 0.5 to 0.7 ng/mL when dosing digoxin in patients with heart failure and reduced EF.
The bilirubin level has been associated with worse outcomes, but it has not been studied as a predictor for the mode of death in patients with systolic heart failure. The Prospective Randomized ...Amlodipine Evaluation Study (PRAISE) cohort (including New York Heart Association class IIIB-IV patients with left ventricular ejection fraction <30%, n = 1,135) was analyzed, divided by bilirubin level: ≤0.6 mg/dl, group 1; >0.6 to 1.2 mg/dl, group 2; and >1.2 mg/dl, group 3. Multivariate Cox proportional hazards models were used to determine the association of bilirubin with the risk of sudden or pump failure death. Total bilirubin was entered as a base 2 log-transformed variable (log2 bilirubin), indicating doubling of the bilirubin level corresponding to each increase in variable value. The higher bilirubin groups had a lower ejection fraction (range 19% to 21%), sodium (range 138 to 139 mmol/L), and systolic blood pressure (range 111 to 120 mm Hg), a greater heart rate (range 79 to 81 beats/min), and greater diuretic dosages (range 86 to 110 furosemide-equivalent total daily dose in mg). The overall survival rates declined with increasing bilirubin (24.3, 31.3, and 44.3 deaths per 100 person-years, respectively, for groups 1, 2, and 3). Although a positive relation was seen between log2 bilirubin and both pump failure risk and sudden death risk, the relation in multivariate modeling was significant only for pump failure mortality (hazard ratio 1.47, 95% confidence interval 1.19 to 1.82, p = 0.0004), not for sudden death mortality (hazard ratio 1.21, 95% confidence interval 0.98 to 1.49, p = 0.08). In conclusion, an increasing bilirubin level was significantly associated with the risk of pump failure death but not for sudden death in patients with severe systolic heart failure.
Abstract Background Hypervolemia and hyponatremia resulting from activation of the neurohormonal system and impairment of renal function are prominent features of decompensated heart failure. Both ...conditions share many pathophysiologic and prognostic features and each has been associated with increased morbidity and mortality. When both conditions coexist, therapeutic options are limited. Methods and Results This review presents a concise digest of the pathophysiology, clinical significance, and pharmacological therapy of hyponatremia complicating heart failure with a special emphasis on vasopressin antagonists and their aquaretic effects in the absence of neurohormonal activation along with their ability to correct hyponatremia. Conclusions Hypervolemia and hyponatremia share many pathophysiologic and prognostic features in heart failure. Vasopressin antagonists provide a viable option for their management and a potentially unique role when both conditions coexists.
Context: Hyponatremia serum sodium concentration (Na+), <135 mEq/liter is the most common fluid and electrolyte abnormality among hospitalized patients. It is frequently caused by the inappropriate ...release of arginine vasopressin.
Objective: The objective of this study was to evaluate the efficacy and safety of oral conivaptan, a vasopressin V1A/V2 receptor antagonist, in patients with euvolemic or hypervolemic hyponatremia.
Design: The study design was a 5-d placebo-controlled, randomized, double-blind study.
Setting: The study was performed at a hospital.
Intervention: Oral conivaptan (40 or 80 mg/d) or placebo was given in two divided doses.
Patients: Seventy-four patients (average baseline serum Na+, 115 to <130 mEq/liter) were studied.
Main Outcome Measure: The main outcome measure was the change from baseline in serum Na+ area under the curve.
Results: The least-squares mean change from baseline in the serum Na+ area under the curve with conivaptan (40 and 80 mg/d) was 2.0-fold (P = 0.03) and 2.5-fold (P < 0.001) greater, respectively, than that with placebo. The median time to achieve a confirmed increase in serum Na+ of 4 mEq/liter or more from baseline was 71.7 h for placebo, 27.5 h for 40 mg/d conivaptan (P = 0.044), and 12.1 h for 80 mg/d conivaptan (P = 0.002). The mean total times during which patients had a serum Na+ level of 4 mEq/liter or more above baseline were 46.5, 69.8, and 88.8 h (P = 0.001), respectively. The least-squares mean change in serum Na+ from baseline to end of treatment was 3.4 mEq/liter for placebo, 6.4 mEq/liter for 40 mg/d conivaptan, and 8.2 mEq/liter for 80 mg/d conivaptan (P = 0.002). A confirmed normal serum Na+ (≥135 mEq/liter) or increase of 6 mEq/liter or more was observed in 48% of patients given placebo, 71% given 40 mg/d conivaptan, and 82% given 80 mg/d conivaptan (P = 0.014). Headache, hypotension, nausea, constipation, and postural hypotension were the most common adverse events.
Conclusion: Oral conivaptan (40 and 80 mg/d) was well tolerated and efficacious in correcting serum Na+ in hyponatremia.
Mechanical dyssynchrony is considered an independent predictor for adverse cardiovascular outcomes in patients with heart failure. However, its importance as a risk factor after myocardial infarction ...is not well defined.
We examined the influence of mechanical dyssynchrony on outcome in patients with left ventricular dysfunction, heart failure, or both after myocardial infarction who were enrolled in the Valsartan in Acute Myocardial Infarction (VALIANT) echocardiography study. B-mode speckle tracking with velocity vector imaging was used to assess ventricular synchrony in 381 patients who had image quality sufficient for analysis. Time to regional peak velocity and time to strain rate were measured among 12 left ventricular segments from the apical 4- and 2- chamber views, and the SDs between all 12 segments were used as a measure of dyssynchrony. The relationships between the SD of time to regional peak velocity and strain rate and clinical outcome of death or heart failure were assessed. In a multivariate Cox model adjusted for clinical and echocardiographic variables, the SD of time to peak velocity (hazard ratio per 10 ms, 1.10; 95% confidence interval, 1.02 to 1.18; P=0.010) and the SD of time to strain rate (hazard ratio per 10 ms, 1.16; 95% confidence interval, 1.06 to 1.27; P=0.001) were independent predictors of death or heart failure.
Left ventricular dyssynchrony is independently associated with increased risk of death or heart failure after myocardial infarction, suggesting that contractile pattern may play a role in post-myocardial infarction prognosis.
Cardiac resynchronization therapy (CRT) alone or combined with an implantable defibrillator (CRT-D) has been shown to improve exercise capacity and quality of life and to reduce heart failure (HF) ...hospitalizations and mortality in patients with New York Heart Association (NYHA) class III and IV HF. There is concern that the device procedure may destabilize these very ill class IV patients. We sought to examine the outcomes of NYHA class IV patients enrolled in the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) trial to assess the potential benefits of CRT and CRT-D.
The COMPANION trial randomized 1520 patients with NYHA class III and IV HF to optimal medical therapy, CRT, or CRT-D. In the class IV patients (n=217), the primary end point of time to death or hospitalization for any cause was significantly improved by both CRT (hazard ratio HR, 0.64; 95% CI, 0.43 to 0.94; P=0.02) and CRT-D (HR, 0.62; 95% CI, 0.42 to 0.90; P=0.01). Time to all-cause death and HF hospitalization was also significantly improved in both CRT (HR, 0.57; 95% CI, 0.37 to 0.87; P=0.01) and CRT-D (HR, 0.49; 95% CI, 0.32 to 0.75; P=0.001) Time to all-cause death trended to an improvement in both CRT (HR, 0.67; 95% CI, 0.41 to 1.10; P=0.11) and CRT-D (HR, 0.63; 95% CI, 0.39 to 1.03; P=0.06). Time to sudden death appeared to be significantly reduced in the CRT-D group (HR, 0.27; 95% CI, 0.08 to 0.90; P=0.03). There was a nonsignificant reduction in time to HF deaths for both CRT (HR, 0.68; 95% CI, 0.34 to 1.37; P=0.28) and CRT-D (HR, 0.79; 95% CI, 0.41 to 1.52; P=0.48).
CRT and CRT-D significantly improve time to all-cause mortality and hospitalizations in NYHA class IV patients, with a trend for improved mortality. These devices should be considered in ambulatory NYHA class IV HF patients similar to those enrolled in COMPANION.
The Next Frontier of Clinical Trials Ghali, Jalal K., MD
Journal of the American College of Cardiology,
04/2012, Letnik:
59, Številka:
17
Journal Article
Recenzirano
When CRT was initially introduced, its benefits had to be proven first, but if we knew then what we know now, we would have selected a QRS complex >=150 ms as a selection criterion and would have ...avoided a scarred area as a lead placement site. ...this trial could serve as a reminder that although when designing clinical trials we need to be as visionary as possible and include as many mechanistic studies as feasible, the reality nevertheless is that there is no alternative to the process of continuing learning from the accumulated clinical experience gained from applying the new intervention and build on this information to refine the original intervention. An important limitation that the authors identified is the failure to use this approach in one-third of the patients being considered for CRT. ...this trial is likely to not only stimulate further innovations in imaging modalities and technical approaches, but also more clinical trials that incorporate the assessment of the role of surgical approaches in their design.
Anemia is a common comorbidity in patients with heart failure (HF) and is associated with poor prognosis. Iron deficiency, with or without anemia, confers increased risk of mortality and morbidity. ...Along with the altered iron metabolism in HF patients, inflammation creates challenges in the interpretation of laboratory parameters used to diagnose anemia in HF. Since the RED-HF trial failed to demonstrate any benefit from the use of erythropoiesis-stimulating agents (ESAs) on mortality or morbidity in HF patients, ESAs are no longer considered a treatment option, although intravenous iron has potential as therapy for anemic and nonanemic HF patients.
Heart failure and diabetes are comorbidities that disproportionately contribute to high morbidity and mortality among Blacks. Further compounding the racial and ethnic disparities in COVID-19 health ...outcomes, Blacks with cardiometabolic diseases are at high risk of experiencing serious complications or mortality from COVID-19. This study aimed to assess how Blacks with heart failure and diabetes navigated chronic care management during the COVID-19 pandemic.
A mixed methods study including in-depth interviews and surveys with adults diagnosed with heart failure and diabetes (n = 17) was conducted in 2021-2022. Verbatim transcripts were analyzed using a thematic analysis approach.
Participants reported that while the pandemic initially caused delays in access to health services, shifts to telemedicine allowed for continued care despite preferences for in-person appointments. Various sources of information were used in different ways to make decisions on how to best reduce health risks due to COVID-19, but individuals and institutions affiliated with science and medicine, or who promoted information from these sources, were considered to be the most trusted sources of information among those who relied on outside guidance when making health-related decisions. Individuals' self-awareness of their own high-risk status and perceived control over their exposure levels to the virus informed what COVID-19 prevention and mitigation strategies people used.
Information backed by scientific data was an important health communication tool that alongside other factors, such as fear of mortality due to COVID-19, encouraged individuals to get vaccinated and adopt other COVID-19 prevention and mitigation behaviors.
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