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Biomedical subjects

Karl Swedberg

Publications and source records attributed to Karl Swedberg.

At least 55 records · Page 3Linked to original sources
PubMed2005

Symptoms in patients with heart failure are prognostic predictors: insights from COMET.

BACKGROUND: Although functional status, as assessed by the New York Heart Association classification, is known to be a powerful prognostic marker in chronic heart failure (CHF), the significance of individual symptoms such as breathlessness and fatigue are unknown. OBJECTIVE: To assess the relative importance of self-reported severity of symptoms as predictors of outcomes in CHF. METHODS AND RESULTS: All 3029 patients randomized in the Carvedilol or Metoprolol European Trial (ie, COMET) study were included in the analysis. Mean follow-up was 58 months. Symptoms were assessed by 5-point scales. In a univariate analysis, worse scores for breathlessness, orthopnea and fatigue were all significantly related to increased mortality (all P < .0001) and development of worsening heart failure. In a multivariate Cox regression analysis including 16 baseline covariates, only the symptom of breathlessness remained significantly related to mortality (risk ratio [RR] 1.14 per unit: 95% CI 1.04-1.26; P = .01). Fatigue, but not breathlessness, remained a significant predictor for developing worsening heart failure (RR 1.09 per unit; 95% CI 1.02-1.18; P = .02). CONCLUSIONS: Fatigue and breathlessness, common symptoms in CHF, have important and independent long-term prognostic implications. Accordingly, symptoms need to be effectively evaluated not only because symptom alleviation is a target for treatment, but also because they guide prognosis in patients with CHF.

Adrenergic beta-Antagonists↗
PubMed2005

Rationale and design of the multicenter, randomized, double-blind, placebo-controlled study to evaluate the Efficacy of Vasopressin antagonism in Heart Failure: Outcome Study with Tolvaptan (EVEREST).

BACKGROUND: Hospitalizations for worsening heart failure due to fluid overload (congestion) are common. Agents that treat congestion without causing electrolyte abnormalities or worsening renal function are needed. Tolvaptan is an oral vasopressin (V 2 ) antagonist that decreases body weight and increases urine volume without inducing renal dysfunction or hypokalemia. The Efficacy of Vasopressin antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial is evaluating mortality, morbidity, and patient-assessed global clinical status in patients treated with tolvaptan compared with standard care. METHODS AND RESULTS: Patients are eligible for inclusion if they have a reduced left ventricular ejection fraction and are hospitalized for worsening heart failure with evidence of systemic congestion. Patients are randomized 1:1 to tolvaptan 30 mg/day or matching placebo for a minimum of 60 days. Time to all-cause mortality and time to cardiovascular mortality or heart failure hospitalization are the coprimary end points. Patient-assessed global clinical status and quality of life are also evaluated. EVEREST will be continued until 1065 deaths occur. As of April 18, 2005, 2260 patients have been enrolled. CONCLUSION: Tolvaptan has been shown to reduce body weight in patients with worsening heart failure without inducing renal dysfunction or causing hypokalemia. The results of EVEREST will determine whether these effects translate into improved clinical outcomes.

Antidiuretic Hormone Receptor Antagonists↗
PubMed2005

Gender makes a difference in the description of dyspnoea in patients with chronic heart failure.

BACKGROUND: Dyspnoea is a common symptom of chronic heart failure (CHF). In the community setting, patients with CHF are most often women. AIM: To examine the impact of gender on the description of dyspnoea and to explore which clinical variables support a diagnosis of CHF. METHODS: From four primary health care centres, 158 patients with CHF were included. Patients were examined with echocardiography and a cardiologist assessed the diagnosis of CHF. The patients filled in a questionnaire containing 11 descriptors of dyspnoea. RESULTS: A diagnosis of CHF was confirmed in 87 (55%) patients (47 males and 40 females). One descriptor, I feel that I am suffocating, was significantly scored higher in CHF patients (p=0.014) as compared to non-CHF patients. Three descriptors, My breath does not go in all the way (p=0.006), I feel that I am suffocating (p=0.040), and I cannot get enough air (p=0.0327) were significantly scored higher among men with CHF, compared to no descriptor among women with CHF. Being male (OR=2.7; CI: 1.3-5.6, p=0.008), having diabetes (OR=5.6; CI: 1.7-18.2, p=0.004), IHD (OR=3.3; CI: 1.3-8.5, p=0.014), and a borderline significance for age (OR=1.04; CI: 0.99-1.08, p=0.058) predicted a confirmed diagnosis of CHF. CONCLUSION: Three descriptors of dyspnoea were associated with CHF among men, whereas no such association was found among women. Our results suggest that gender is an important factor and should-together with age, underlying heart disease, and diabetes-be taken into account when symptoms are evaluated in the diagnosis of CHF in primary care.

Age Factors↗
PubMed2005

Exchange of beta-blockers in heart failure patients. Experiences from the poststudy phase of COMET (the Carvedilol or Metoprolol European Trial).

BACKGROUND: The Carvedilol or Metoprolol European Trial (COMET) reported a significant survival benefit for carvedilol, a beta1-, beta2- and alpha1-blocker, vs. metoprolol tartrate, a beta1-selective blocker, in patients with mild-to-severe chronic heart failure (CHF). Patients on treatment with metoprolol might benefit from switching to carvedilol. AIM: To investigate the safety and tolerability of switching beta-blockers in CHF. METHODS: At the end of COMET, the Steering Committee recommended that study medication was stopped without unblinding, and patients were commenced on open-label beta-blockade at a dose equivalent to half the dose of blinded therapy, with subsequent titration to target or maximum tolerated dose. Patients were followed for 30 days. RESULTS: 1321 out of 1440 patients were transitioned to open-label treatment (76.8% to carvedilol). Serious adverse and CHF-related events were respectively 9.4% and 4.7% in those switching from carvedilol to metoprolol and 3.1% and 1.5% in patients switching from metoprolol to carvedilol. Patients who switched from carvedilol to metoprolol showed the highest mortality or hospitalisation rate (12.3%) in comparison with those who switched from metoprolol to carvedilol (3.1%, p<0.001) or who stayed on the same drug (carvedilol: 2.5%, p<0.001; metoprolol: 4.2%, p=0.04). Reducing the initial dose of the second beta-blocker maximised the safety of this strategy. Event rate was higher in patients with more severe heart failure and in those withdrawing from beta-blockade. CONCLUSION: Our data show that switching beta-blockers is a practical, safe and well-tolerated strategy to optimise treatment of CHF. Patients who switched to carvedilol showed the lowest rate of adverse events. A closer clinical monitoring is recommended during transition in high-risk patients.

Adrenergic beta-Antagonists↗
PubMed2005

Patient perception of the effect of treatment with candesartan in heart failure. Results of the candesartan in heart failure: assessment of reduction in mortality and morbidity (CHARM) programme.

AIMS: To evaluate the effect of the angiotensin receptor blocker candesartan on patients' perception of symptoms, using the McMaster Overall treatment evaluation (OTE), in a broad spectrum of patients with chronic heart failure (CHF). METHODS AND RESULTS: Patients with symptomatic CHF, randomised in the CHARM Programme in North America (n=2498), were studied. OTE was assessed at baseline, at 6, 14 and 26 months and the patient's final or closing visit. Patient's status was classified as "improved (score +1 to +7)", "unchanged (score 0)" or "deteriorated (score -1 to -7)" at the end of the study compared to baseline. Both a simple "last visit carried forward" (LVCF) analysis and "worst rank carried forward" (WRCF) analysis (where patients who died were allocated the worst OTE score) were used. In the LVCF analysis, compared to placebo, more candesartan patients improved (37.7% versus 33.5%) and fewer worsened (10.8% versus 12.0%) in OTE (p=0.017). The WRCF analysis also showed better overall OTE scores with candesartan compared to placebo (p=0.029). There was no heterogeneity in the response to candesartan between the CHARM component trials or across four exploratory sub-groups (age, sex, NYHA class and beta-blocker). CONCLUSIONS: Candesartan was shown to be better than placebo, when using the McMaster OTE to measure patient perception of treatment. More patients treated with candesartan reported improvement and fewer reported deterioration. This benefit was obtained when candesartan was added to extensive background therapy and is consistent with the benefits of candesartan on NYHA class, hospital admission for worsening heart failure and mortality.

Aged↗
PubMed2005

Practical recommendations for the use of ACE inhibitors, beta-blockers, aldosterone antagonists and angiotensin receptor blockers in heart failure: putting guidelines into practice.

Surveys of prescribing patterns in both hospitals and primary care have usually shown delays in translating the evidence from clinical trials of pharmacological agents into clinical practice, thereby denying patients with heart failure (HF) the benefits of drug treatments proven to improve well-being and prolong life. This may be due to unfamiliarity with the evidence-base for these therapies, the clinical guidelines recommending the use of these treatments or both, as well as concerns regarding adverse events. ACE inhibitors have long been the cornerstone of therapy for systolic HF irrespective of aetiology. Recent trials have now shown that treatment with beta-blockers, aldosterone antagonists and angiotensin receptor blockers also leads to substantial improvements in outcome. In order to accelerate the safe uptake of these treatments and to ensure that all eligible patients receive the most appropriate medications, a clear and concise set of clinical recommendations has been prepared by a group of clinicians with practical expertise in the management of HF. The objective of these recommendations is to provide practical guidance for non-specialists, in order to increase the use of evidenced based therapy for HF. These practical recommendations are meant to serve as a supplement to, rather than replacement of, existing HF guidelines.

Adrenergic beta-Antagonists↗
PubMed2005

Exploring symptoms in chronic heart failure.

Symptoms in patients with chronic heart failure (CHF) are the cry for help, reflecting not only the physical aspects of the disease but the impact on lifestyle, anxiety, depression and expectations of the patient. Studies consistently show a difference in patients' self-assessed functional classification compared to investigator reported NYHA classification. Moreover, patient self-assessed symptoms have recently been shown to independently predict hospitalisation and mortality over 5 years. Recognition of symptoms and appreciation of their importance justifies the use of a structured assessment in order to provide optimal medical care for patients with CHF. A model of how to structure symptom assessment equally with signs is presented in this paper.

Dyspnea↗
PubMed2005

Cardiac troponin I, a possible predictor of survival in patients with stable congestive heart failure.

BACKGROUND: Cardiac troponin I (cTnI) has been validated as a sensitive and specific marker of myocyte damage, and is elevated in some patients with congestive heart failure. OBJECTIVE: To assess the relationship between elevated levels of cTnI and survival in stable patients with congestive heart failure. PATIENTS AND METHODS: It was assessed whether detectable serial levels of cTnI were associated with mortality in 211 patients with stable, severe heart failure at entry and one month into the Prospective Randomized Flosequinan Longevity Evaluation (PROFILE) study. Of these patients, 66 also had measurements taken at 12 months. RESULTS: Patients were New York Heart Association (NYHA) class III (n=197) or IV (n=14), with a baseline left ventricular ejection fraction of 22+/-7% (range 8% to 35%). Patients with a detectable level of cTnI at one month had an increased mortality (OR 2.608 [95% CI 1.061 to 6.409]; P=0.037). The association between mortality and detectable cTnI levels at baseline or 12 months did not reach statistical significance. Patients with a cTnI level that rose or remained elevated between baseline and one month had a higher mortality rate (50%) than those in whom the cTnI level fell (9%) between baseline and one month (P=0.025). In a multivariate model of survival that included sex, treatment, age, left ventricular ejection fraction, NYHA class and creatinine, only detectable levels of cTnI at one month were associated with survival (P=0.037). CONCLUSIONS: cTnI is released in stable, chronic heart failure and is associated with a poor prognosis, independent of other important risk factors. The risk is particularly elevated when detectable cTnI levels rise or remain elevated over time.

Adult↗
PubMed2004

Prognostic risk of atrial fibrillation in acute myocardial infarction complicated by left ventricular dysfunction: the OPTIMAAL experience.

AIMS: The present study aimed to determine the frequency and the impact on clinical outcome of atrial fibrillation (AF) in patients with acute myocardial infarction (AMI) and left ventricular dysfunction. METHODS AND RESULTS: In the OPTIMAAL trial, 5477 patients with AMI and signs of left ventricular dysfunction were included. At baseline, 655 patients (12%) had AF, and 345 (7.2%) developed new-onset AF during follow-up (2.7 +/- 0.9 years). Older patients, patients with history of angina and worse Killip class had and developed AF more frequently (P < 0.001). Patients with AF at baseline were at increased risk relative to those without AF for mortality [adjusted hazard ratio (HR) of 1.32, P = 0.001] and for stroke (HR 1.77, P < 0.001). New-onset AF was associated with increased subsequent mortality for the first 30 days following randomization (HR 3.83, P < 0.001) and the entire trial period (HR 1.82, P < 0.001). Risk of stroke was increased for the first 30 days (HR 14.6, P < 0.001) and for the whole trial period (HR 2.29, P < 0.001). CONCLUSION: AF is frequently observed in patients with AMI complicated by heart failure. Current AF, and the development of new AF soon after AMI, is associated with increased risk of death and stroke.

Aged↗
PubMed2004

Mortality and morbidity reduction with Candesartan in patients with chronic heart failure and left ventricular systolic dysfunction: results of the CHARM low-left ventricular ejection fraction trials.

BACKGROUND: Patients with symptomatic chronic heart failure (CHF) and reduced left ventricular ejection fraction (LVEF) have a high risk of death and hospitalization for CHF deterioration despite therapies with angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and even an aldosterone antagonist. To determine whether the angiotensin-receptor blocker (ARB) candesartan decreases cardiovascular mortality, morbidity, and all-cause mortality in patients with CHF and depressed LVEF, a prespecified analysis of the combined Candesartan in Heart Failure Assessment of Reduction in Mortality and morbidity (CHARM) low LVEF trials was performed. CHARM is a randomized, double-blind, placebo-controlled, multicenter, international trial program. METHODS AND RESULTS: New York Heart Association (NYHA) class II through IV CHF patients with an LVEF of < or =40% were randomized to candesartan or placebo in 2 complementary parallel trials (CHARM-Alternative, for patients who cannot tolerate ACE inhibitors, and CHARM-Added, for patients who were receiving ACE inhibitors). Mortality and morbidity were determined in 4576 low LVEF patients (2289 candesartan and 2287 placebo), titrated as tolerated to a target dose of 32 mg once daily, and observed for 2 to 4 years (median, 40 months). The primary outcome (time to first event by intention to treat) was cardiovascular death or CHF hospitalization for each trial, with all-cause mortality a secondary end point in the pooled analysis of the low LVEF trials. Of the patients in the candesartan group, 817 (35.7%) experienced cardiovascular death or a CHF hospitalization as compared with 944 (41.3%) in the placebo group (HR 0.82; 95% CI 0.74 to 0.90; P<0.001) with reduced risk for both cardiovascular deaths (521 [22.8%] versus 599 [26.2%]; HR 0.84 [95% CI 0.75 to 0.95]; P=0.005) and CHF hospitalizations (516 [22.5%] versus 642 [28.1%]; HR 0.76 [95% CI 0.68 to 0.85]; P<0.001). It is important to note that all-cause mortality also was significantly reduced by candesartan (642 [28.0%] versus 708 [31.0%]; HR 0.88 [95% CI 0.79 to 0.98]; P=0.018). No significant heterogeneity for the beneficial effects of candesartan was found across prespecified and subsequently identified subgroups including treatment with ACE inhibitors, beta-blockers, an aldosterone antagonist, or their combinations. The study drug was discontinued because of adverse effects by 23.1% of patients in the candesartan group and 18.8% in the placebo group; the reasons included increased creatinine (7.1% versus 3.5%), hypotension (4.2% versus 2.1%), and hyperkalemia (2.8% versus 0.5%), respectively (all P<0.001). CONCLUSIONS: Candesartan significantly reduces all-cause mortality, cardiovascular death, and heart failure hospitalizations in patients with CHF and LVEF < or =40% when added to standard therapies including ACE inhibitors, beta-blockers, and an aldosterone antagonist. Routine monitoring of blood pressure, serum creatinine, and serum potassium is warranted.

Aged↗