Angiotensin-converting enzyme (ACE) inhibitors have been shown to attenuate left ventricular (LV) enlargement in association with reducing mortality after myocardial infarction (MI). Preclinical data ...suggest that angiotensin receptor blockers (ARBs) may have similar structural and functional effects after MI. The Valsartan in Acute Myocardial Infarction (VALIANT) Echo study was designed to test the hypothesis that the ARB valsartan, either alone or in combination with captopril, could attenuate progressive LV enlargement or improve LV ejection fraction to a greater extent than captopril alone.
Six hundred ten patients enrolled in the main VALIANT study who experienced MI and evidence of LV dysfunction, heart failure, or both were enrolled in the VALIANT Echo study. Patients were randomized to receive valsartan 160 mg PO BID, captopril 50 mg PO TID, or valsartan 80 mg PO BID plus captopril 50 mg PO TID between 1 and 10 days after MI. Six hundred three patients had echocardiograms of sufficient quality for quantitative analysis. Echocardiograms were digitized, and endocardial borders were traced manually from 2 short-axis and 2 apical views. Ventricular volumes, ejection fractions, combined areas, and infarct segment length were measured, and changes in echocardiographic measures from baseline to 20 months were compared between treatment groups. Baseline clinical and echocardiographic characteristics were similar in the 3 treatment arms. The changes from baseline to 20 months in all echocardiographic parameters were similar in all 3 treatment arms. Baseline echocardiographic measures of ejection fraction, end-diastolic volume, and infarct segment length were highly predictive of outcomes including total mortality, death or hospitalization for heart failure, or death or any cardiovascular event (heart failure, MI, stroke, resuscitated sudden death), even after adjustment for known covariates.
Treatment with the ACE inhibitor captopril, valsartan, or the combination of captopril plus valsartan resulted in similar changes in cardiac volume, ejection fraction, and infarct segment length between baseline and 20 months after MI. Baseline echocardiographic measures were powerfully and independently predictive of all major outcomes.
Aims
Volume overload is the dominant feature of decompensated heart failure (HF) and it often results in adverse clinical outcomes. Vasopressin receptor antagonists such as lixivaptan may provide ...effective volume unloading. This study assessed weight loss after 1 day and 8 weeks of treatment with lixivaptan in outpatients with HF and volume overload.
Methods and results
This phase II, 8‐week, multicentre, double‐blind, parallel‐group study randomized participants (2:1) to receive lixivaptan 100 mg or placebo once daily (in addition to standard HF therapy). Body weight and cardiovascular assessments were made at baseline, Day 1 (not cardiovascular), Weeks 1, 2, 4, and 8, and 7 days post‐treatment. The Trail‐making Test, part B (TMT‐B) and the Medical Outcomes Survey 6‐item cognitive function scale (MOS‐6) were assessed at baseline and Week 4. The study randomized 170 participants (lixivaptan, n = 111; placebo, n = 59). Most (97.1%) were receiving pharmacological therapy for HF at baseline. Demographic characteristics were generally similar between the two groups. Body weight decreased significantly from baseline to Day 1 with lixivaptan vs. placebo (least‐square mean change ± standard error: − 0.38 ± 0.08 kg vs. +0.13 ± 0.11 kg; P < 0.001) and at Weeks 1, 2, and 4 (P < 0.01). Cardiovascular changes were generally similar in both groups, though orthopnoea and dyspnoea improved in the lixivaptan group vs. placebo. The TMT‐B and MOS‐6 showed no significant differences between groups. Lixivaptan was well tolerated—thirst and polyuria occurred more frequently vs. placebo.
Conclusions
In outpatients with HF and volume overload, lixivaptan 100 mg once daily, when added to standard therapy, reduced body weight, improved dyspnoea and orthopnoea, and was well tolerated.
Trial registration: NCT01055912
Background: The epidemiology and clinical implications of asymptomatic atrial tachyarrhythmias (AT) including both atrial fibrillation and flutter in pacemaker recipients with and without arrhythmia ...history are not well understood. The Atrial High Rate Episodes (A‐HIRATE) in Pacemaker Patients Trial was designed to identify and compare the incidence of AT in patients with and without previously diagnosed AT and a standard indication for dual chamber pacing, and to provide useful diagnostic information for clinical management.
Methods: Four hundred twenty‐seven patients were implanted with a pacemaker (Kappa 7‐900, Medtronic, Inc., Minneapolis, MN, USA) capable of detecting and storing multiple atrial high rate episodes (AHRE) and followed for 2 years. Group I included 331 patients without prior history of AT and Group II included 96 patients with prior AT history.
Results: Pacemaker diagnostics appropriately detected 93% of reviewed AHRE. The rate of occurrence of first AHRE was significantly higher (P < 0.0001) in Group II patients, as was average AHRE burden. The rate of first AHRE occurrence was 88.6% for patients in Group II and 53.8% in Group I at 24 months post‐implant. The rate of AHRE occurrence was similar in both groups after the first month post‐implant. The majority of stored AHRE were asymptomatic; symptoms did not correspond to an actual AHRE in most patients.
Conclusions: The incidence of AT in pacemaker recipients is high. Most device‐detected AHRE are asymptomatic. Prior history of AT is associated with higher arrhythmia burden. AHRE diagnostics have a high positive predictive value for identifying AT events.
Anemia and iron deficiency are quite prevalent in patients with heart failure (HF) and may overlap. Both anemia and iron deficiency are associated with worse symptoms and adverse clinical outcomes. ...In the past few years, there has been an enormous interest in the subject of iron deficiency and its management in patients with HF. In this review, the etiology and relevance of iron deficiency, iron metabolism in the setting of HF, studies on iron supplementation in patients with HF and potential cardiovascular effects of subclinical iron overload are discussed.
Abstract Introduction Red-cell distribution width (RDW) has been identified as a novel prognostic marker in heart failure patients. However, evidence is limited for its predictive value in the ...setting of patients hospitalized with decompensated heart failure (DHF) and no data are available for African Americans (AA). Methods and Results Data that included baseline characteristics, laboratory findings, and discharge medications were collected retrospectively on a total of 789 patients with DHF (mean age 62.7 ± 15.1 years, 50% males and 80% AA), admitted to an urban medical center between January 2007 and August 2007, 145 (18.38%) died during median follow-up of 573 days. Unadjusted and adjusted Cox-proportional hazard models were used to analyze predictive value of discharge RDW on mortality. There was a significant negative association between RDW and statin use, blood hemoglobin levels and mean corpuscular volume (MCV); whereas serum creatinine and blood urea nitrogen (BUN) increased with increasing RDW. A statistically significant graded increase in all-cause mortality with higher RDW quartiles (lowest vs highest quartile), independent of hemoglobin and creatinine levels, was found for all patients (adjusted hazard ratio HR 3.21; 95% confidence interval CI: 1.77–5.83, P < .05) for AAs (adjusted HR 2.92; 95% CI: 1.50–5.71, P < .05) and for non-AAs (adjusted HR-1.27, 95% CI: 1.03–1.55, P = 0.019; RDW evaluated as continuous variable). Conclusion Discharge RDW is an independent predictor of all-cause mortality in predominantly AA patients hospitalized with DHF. Further research is warranted to delineate underlying pathophysiological mechanisms including the association between statin use and RDW.
Abstract Background Limited information is available on the risk and impact of renal dysfunction on the response to β-blockade and mode of death in systolic heart failure (HF). Methods and Results ...Renal function was estimated with glomerular filtration rate (eGFR) using the simplified Modification of Diet in Renal Disease (MDRD) equation. Patients from the Metoprolol CR/XL Controlled Randomized Intervention Trial in Chronic HF (MERIT-HF) were divided into 3 renal function subgroups (MDRD formula): eGFRMDRD > 60 (n = 2496), eGFRMDRD 45 to 60 (n = 976), and eGFRMDRD < 45 mL/min per 1.73m2 body surface area (n = 493). Hazard ratio (HR) was estimated with Cox proportional hazards models adjusted for prespecified risk factors. Placebo patients with eGFR < 45 had significantly higher risk than those with eGFR > 60: HR for all-cause mortality, 1.90 (95% confidence interval CI, 1.28 to 2.81) comparing placebo patients with eGFR < 45 and eGFR > 60, and for the combined end point of all-cause mortality/hospitalization for worsening HF (time to first event): HR, 1.91 (95% CI, 1.44 to 2.53). No significant increase in risk with deceased renal function was observed for those randomized to metoprolol controlled release (CR)/extended release (XL) due to a highly significant decrease in risk on metoprolol CR/XL in those with eGFR < 45. For total mortality, metoprolol CR/XL vs placebo: HR, 0.41 (95% CI. 0.25 to 0.68; P < .001) in those with eGFR < 45 compared with HR, 0.71 (95% CI, 0.54 to 0.95; P < .021) for those with eGFR > 60; corresponding data for the combined end point was HR, 0.44 (95% CI, 0.31 to 0.63; P < .0001) and HR, 0.75 (0.62 to 0.92; P = .005, respectively; P = .095 for interaction by treatment for total mortality; P = .011 for combined end point). Metoprolol CR/XL was well tolerated in all 3 renal function subgroups. Conclusions Renal function as estimated by eGFR was a powerful predictor of death and hospitalizations from worsening HF. Metoprolol CR/XL was at least as effective in reducing death and hospitalizations for worsening HF in patients with eGFR < 45 as in those with eGFR > 60.
The diagnosis of diastolic heart failure is generally made in patients who have the signs and symptoms of heart failure and a normal left ventricular (LV) ejection fraction. Whether the diagnosis ...also requires an objective measurement of parameters that reflect the diastolic properties of the ventricle has not been established.
We hypothesized that the vast majority of patients with heart failure and a normal ejection fraction exhibit abnormal LV diastolic function. We tested this hypothesis by prospectively identifying 63 patients with a history of heart failure and an echocardiogram suggesting LV hypertrophy and a normal ejection fraction; we then assessed LV diastolic function during cardiac catheterization. All 63 patients had standard hemodynamic measurements; 47 underwent detailed micromanometer and echocardiographic-Doppler studies. The LV end-diastolic pressure was >16 mm Hg in 58 of the 63 patients; thus, 92% had elevated end-diastolic pressure (average, 24+/-8 mm Hg). The time constant of LV relaxation (average, 51+/-15 ms) was abnormal in 79% of the patients. The E/A ratio was abnormal in 48% of the patients. The E-wave deceleration time (average, 349+/-140 ms) was abnormal in 64% of the patients. One or more of the indexes of diastolic function were abnormal in every patient.
Objective measurement of LV diastolic function serves to confirm rather than establish the diagnosis of diastolic heart failure. The diagnosis of diastolic heart failure can be made without the measurement of parameters that reflect LV diastolic function.
Tolvaptan Ghali, Jalal K; Hamad, Bashar; Yasothan, Uma ...
Nature reviews. Drug discovery,
08/2009, Letnik:
8, Številka:
8
Journal Article
Recenzirano
In May 2009, tolvaptan (Samsca; Otsuka), a selective vasopressin V(2) receptor antagonist, was approved by the US FDA for the treatment of clinically significant hypervolaemic and euvolaemic ...hyponatraemia.
PDF
