Mixed messages? Exposure to reports about alcohol's suggested cardiovascular effects and hazardous alcohol use: a cross-sectional study of patients in cardiology care.

BACKGROUND: Hazardous alcohol use is a leading risk factor for disability and death, yet observational studies have also reported reduced cardiovascular disease mortality among regular, low-level drinkers. Such findings are refuted by more recent research, yet have received significant media coverage. We aimed to explore: (1) how patients with cardiovascular diseases access health information about moderate drinking and cardiovascular health; (2) the perceived messages these sources convey, and (3) associations with own level of alcohol use. METHODS: We conducted a cross-sectional survey of patients in cardiology services at three hospitals in Sweden. The study outcome was hazardous alcohol use, assessed using the AUDIT-C questionnaire and defined as ≥ 3 in women and ≥ 4 in men. The exposure was accessing information sources suggesting that moderate alcohol consumption can be good for the heart, as opposed to accessing information that alcohol is bad for the heart. Health information sources were described using descriptive statistics. Gender, age and education were adjusted for in multiple logistic regression analyses. RESULTS: A total of 330 (66.3%) of 498 patients (mean age 70.5 years, 65% males) who had heard that drinking moderately can affect the heart described being exposed to reports that moderate alcohol use can be good for the heart, and 108 (21.7%) met criteria for hazardous alcohol use. Health information sources included newspapers (32.9%), television (29.2%), healthcare staff (13.4%), friends/family (11.8%), social media (8.9%) and websites (3.7%). Participants indicated that most reports (77.9%) conveyed mixed messages about the cardiovascular effects of moderate drinking. Exposure to reports of healthy heart effects, or mixed messages about the cardiovascular effects of alcohol, was associated with increased odds of hazardous alcohol use (OR = 1.67, 95%CI = 1.02-2.74). CONCLUSIONS: This study suggests that many patients in cardiology care access health information about alcohol from media sources, which convey mixed messages about the cardiovascular effects of alcohol. Exposure to reports that moderate drinking has protective cardiovascular effects, or mixed messages about the cardiovascular effects of alcohol, was associated with increased odds of hazardous alcohol use. Findings highlight a need for clear and consistent messages about the health effects of alcohol.

Heart failure: the grim reaper of the cardio-renal-metabolic triad.

AIMS: Current understanding of the prognosis for patients with chronic kidney disease (CKD) and overlapping cardio-renal-metabolic components, specifically heart failure (HF) and diabetes mellitus (DM), remains limited. While previous studies have explored the interactions between CKD, HF, and DM, they have predominantly focused on cohorts of HF or DM patients. This study aims to fill this gap by investigating the long-term outcomes and treatment patterns in a cohort of CKD patients, particularly those with coexisting HF and DM. METHODS AND RESULTS: We analysed data from the Swedish national CKD patient cohort, the Swedish Renal Registry, with a follow-up period extending up to 10 years. The study examined the risks of all-cause mortality, major adverse cardiovascular events (MACE)-defined as a composite of non-fatal myocardial infarction, hospitalization for congestive HF, non-fatal stroke, or cardiovascular death-and the initiation of kidney replacement therapy (KRT). Analyses were conducted using Cox proportional hazards and competing risk models. Among the 27 647 patients, 48% had CKD alone, 12% had CKD with HF, 27% had CKD with DM, and 13% had CKD with both HF and DM. After 5 years, mortality rates were 23% for patients with CKD, 30% for those with CKD/DM, 54% for CKD/HF, and 55% for CKD/HF/DM. The 10 year absolute risk of MACE was 28% for CKD alone, 35% for CKD/DM, 67% for CKD/HF, and 73% for CKD/HF/DM. The adjusted hazard ratio (HR) for mortality was approximately three times higher in patients with any HF combination, with HRs of 2.57 [95% confidence interval (CI) 2.43-2.71] for CKD/HF and 3.22 (95% CI 3.05-3.39) for CKD/HF/DM, compared with CKD alone. The impact of HF on MACE prognosis was even more pronounced, with adjusted sub-hazard ratios (SHRs) of 3.33 (95% CI 3.14-3.53) for CKD/HF and 4.26 (95% CI 4.04-4.50) for CKD/HF/DM. Additionally, CKD patients diagnosed with HF were less likely to commence KRT, and the risk of death prior to KRT initiation was roughly twice as high for these groups, with SHRs of 2.05 (95% CI 1.93-2.18) for CKD + HF and 2.43 (95% CI 2.29-2.58) for CKD + HF + DM. CONCLUSIONS: In a cohort of CKD patients, having HF contributes substantially to increased mortality and the risk of MACE, and these patients are less likely to start KRT. These findings highlight the urgent need for targeted therapeutic strategies and management plans for CKD patients, particularly those with concurrent HF, to enhance patient prognosis.

Feasibility of alcohol interventions in cardiology: A qualitative study of clinician perspectives in Sweden.

AIM: To identify barriers and facilitators to implementing alcohol screening and brief interventions (SBI) in cardiology services. METHODS AND RESULTS: Qualitative study. Individual, semi-structured interviews were conducted with 24 clinical cardiology staff (doctors, nurses, assistant nurses) of varying experience levels, and from various clinical settings (high dependency unit, ward, outpatient clinic), in three regions of Sweden. Reflexive thematic analysis was used, with deductive coding applying the Capability, Opportunity, Motivation (COM-B) theoretical framework. A total of 41 barriers and facilitators were identified, including twelve related to capability, nine to opportunity, and 20 to motivation. Four themes were developed: 1. Uncharted territory, where clinicians expressed a need to address alcohol use but lacked knowledge and a roadmap for implementing SBI; 2. Cardiology as a cardiovascular specialty, where tasks were prioritized according to established roles; 3. Alcohol stigma, where alcohol was reported to be a sensitive topic that staff avoid discussing with patients; 4. Window of opportunity, where staff expressed potential for implementing SBI in routine cardiology care. CONCLUSION: Findings suggest that opportunities exist for early identification and follow-up of hazardous alcohol use within routine cardiology care. Several barriers, including low knowledge, stigma, a lack of ownership, and a greater focus on other risk factors must be addressed prior to the implementation of SBI in cardiology. To meet current clinical guidelines, there is a need to increase awareness and to improve pathways to addiction care. In addition, there may be a need for clinicians dedicated to alcohol interventions within cardiology services. REGISTRATION: OSF (osf.io/hx3ts).

Association between central haemodynamics and renal function in advanced heart failure: a nationwide study from Sweden.

AIMS: Renal dysfunction in patients with heart failure (HF) has traditionally been attributed to declining cardiac output and renal hypoperfusion. However, other central haemodynamic aberrations may contribute to impaired kidney function. This study assessed the relationship between invasive central haemodynamic measurements from right-heart catheterizations and measured glomerular filtration rate (mGFR) in advanced HF. METHODS AND RESULTS: All patients referred for heart transplantation work-up in Sweden between 1988 and 2019 were identified through the Scandiatransplant organ-exchange organization database. Invasive haemodynamic variables and mGFR were retrieved retrospectively. A total of 1001 subjects (49 ± 13 years; 24% female) were eligible for the study. Analysis of covariance adjusted for age, sex, and centre revealed that higher right atrial pressure (RAP) displayed the strongest relationship with impaired GFR [ß coefficient -0.59; 95% confidence interval (CI) -0.69 to -0.48; P < 0.001], followed by lower mean arterial pressure (MAP) (ß coefficient 0.29; 95% CI 0.14-0.37; P < 0.001), and finally reduced cardiac index (ß coefficient 3.51; 95% CI 2.14-4.84; P < 0.003). A combination of high RAP and low MAP was associated with markedly worse mGFR than any other RAP/MAP profile, and high renal perfusion pressure (RPP, MAP minus RAP) was associated with superior renal function irrespective of the degree of cardiac output. CONCLUSIONS: In patients with advanced HF, high RAP contributed more to impaired GFR than low MAP. A higher RPP was more closely related to GFR than was high cardiac index.

Scoring of medial arterial calcification predicts cardiovascular events and mortality after kidney transplantation.

BACKGROUND: Progression of vascular calcification causes cardiovascular disease, which is the most common cause of death in chronic kidney failure and after kidney transplantation (KT). The prognostic impact of the extent of medial vascular calcification at KT is unknown. METHODS: In this prospective cohort study, we investigated the impact of medial calcification compared to a mix of intimal and medial calcification represented by coronary artery calcification (CAC score) and aortic valve calcification in 342 patients starting on kidney failure replacement therapy. The primary outcomes were cardiovascular events (CVE) and death. The median follow-up time was 6.4 years (interquartile range 3.7-9.6 years). Exposure was CAC score and arteria epigastrica medial calcification scored as none, mild, moderate, or severe by a pathologist at time of KT (n = 200). We divided the patients according to kidney failure replacement therapy during follow-up, that is, living donor KT, deceased donor KT, or dialysis. RESULTS: Moderate to severe medial calcification in the arteria epigastrica was associated with higher mortality (p = 0.001), and the hazard ratio for CVE was 3.1 (95% confidence interval [CI] 1.12-9.02, p < 0.05) compared to no or mild medial calcification. The hazard ratio for 10-year mortality in the dialysis group was 33.6 (95% CI, 10.0-113.0, p < 0.001) compared to living donor recipients, independent of Framingham risk score and prevalent CAC. CONCLUSION: Scoring of medial calcification in the arteria epigastrica identified living donor recipients as having 3.1 times higher risk of CVE, independent of traditional risk factors. The medial calcification score could be a reliable method to identify patients with high and low risk of CVE and mortality following KT.

COVID-19 in solid organ transplant recipients: A national cohort study from Sweden.

Solid organ transplant (SOT) recipients run a high risk for adverse outcomes from COVID-19, with reported mortality around 19%. We retrospectively reviewed all known Swedish SOT recipients with RT-PCR confirmed COVID-19 between March 1 and November 20, 2020 and analyzed patient characteristics, management, and outcome. We identified 230 patients with a median age of 54.0 years (13.2), who were predominantly male (64%). Most patients were hospitalized (64%), but 36% remained outpatients. Age >50 and male sex were among predictors of transition from outpatient to inpatient status. National early warning Score 2 (NEWS2) at presentation was higher in non-survivors. Thirty-day all-cause mortality was 9.6% (15.0% for inpatients), increased with age and BMI, and was higher in men. Renal function decreased during COVID-19 but recovered in most patients. SARS-CoV-2 antibodies were identified in 78% of patients at 1-2 months post-infection. Nucleocapsid-specific antibodies decreased to 38% after 6-7 months, while spike-specific antibody responses were more durable. Seroprevalence in 559 asymptomatic patients was 1.4%. Many patients can be managed on an outpatient basis aided by risk stratification with age, sex, and NEWS2 score. Factors associated with adverse outcomes include older age, male sex, greater BMI, and a higher NEWS2 score.

Comorbidities and cause-specific outcomes in heart failure across the ejection fraction spectrum: A blueprint for clinical trial design.

BACKGROUND: Comorbidities may differently affect treatment response and cause-specific outcomes in heart failure (HF) with preserved (HFpEF) vs. mid-range/mildly-reduced (HFmrEF) vs. reduced (HFrEF) ejection fraction (EF), complicating trial design. In patients with HF, we performed a comprehensive analysis of type 2 diabetes (T2DM), atrial fibrillation (AF) chronic kidney disease (CKD), and cause-specific outcomes. METHODS AND RESULTS: Of 42,583 patients from the Swedish HF registry (23% HFpEF, 21% HFmrEF, 56% HFrEF), 24% had T2DM, 51% CKD, 56% AF, and 8% all three comorbidities. HFpEF had higher prevalence of CKD and AF, HFmrEF had intermediate prevalence of AF, and prevalence of T2DM was similar across the EF spectrum. Patients with T2DM, AF and/or CKD were more likely to have also other comorbidities and more severe HF. Risk of cardiovascular (CV) events was highest in HFrEF vs. HFpEF and HFmrEF; non-CV risk was highest in HFpEF vs. HFmrEF vs. HFrEF. T2DM increased CV and non-CV events similarly but less so in HFpEF. CKD increased CV events somewhat more than non-CV events and less so in HFpEF. AF increased CV events considerably more than non-CV events and more so in HFpEF and HFmrEF. CONCLUSION: HFpEF is distinguished from HFmrEF and HFrEF by more comorbidities, non-CV events, but lower effect of T2DM and CKD on events. CV events are most frequent in HFrEF. To enrich for CV vs. non-CV events, trialists should not exclude patients with lower EF, AF and/or CKD, who report higher CV risk.

Chronic pancreatitis and the heart disease: Still terra incognita?

BACKGROUND: It has been suggested that chronic pancreatitis (CP) may be an independent risk factor for development of cardiovascular disease (CVD). At the same time, it seems that congestive heart failure (CHF) and CP share the responsibility for the development of important clinical conditions such as sarcopenia, cachexia and malnutrition due to development of cardiac cachexia and pancreatic exocrine insufficiency (PEI), respectively. AIM: To explore the evidence regarding the association of CP and heart disease, more specifically CVD and CHF. METHODS: A systematic search of MEDLINE, Web of Science and Google Scholar was performed by two independent investigators to identify eligible studies where the connection between CP and CVD was investigated. The search was limited to articles in the English language. The last search was run on the 1st of May 2019. The primary outcomes were: (1) Incidence of cardiovascular event [acute coronary syndrome (ACS), chronic coronary disease, peripheral arterial lesions] in patients with established CP; and (2) Incidence of PEI in patients with CHF. RESULTS: Out of 1166 studies, only 8 were eligible for this review. Studies regarding PEI and CHF showed an important incidence of PEI as well as associated malabsorption of nutritional markers (vitamin D, selenium, phosphorus, zinc, folic acid, and prealbumin) in patients with CHF. However, after substitution of pancreatic enzymes, it seems that, at least, loss of appetite was attenuated. On the other side, studies investigating cardiovascular events in patients with CP showed that, in CP cohort, there was a 2.5-fold higher incidence of ACS. In another study, patients with alcohol-induced CP with concomitant type 3c diabetes had statistically significant higher incidence of carotid atherosclerotic plaques in comparison to patients with diabetes mellitus of other etiologies. Earlier studies demonstrated a marked correlation between the clinical symptoms in CP and chronic coronary insufficiency. Also, statistically significant higher incidence of arterial lesions was found in patients with CP compared to the control group with the same risk factors for atherosclerosis (hypertension, smoking, dyslipidemia). Moreover, one recent study showed that PEI is significantly associated with the risk of cardiovascular events in patients with CP. CONCLUSION: Current evidence implicates a possible association between PEI and malnutrition in patients with CHF. Chronic pancreatic tissue hypoxic injury driven by prolonged splanchnic hypoperfusion is likely to contribute to malnutrition and cachexia in patients with CHF. On the other hand, CP and PEI seem to be an independent risk factor associated with an increased risk of cardiovascular events.

Incidence of, Associations With and Prognostic Impact of Worsening Renal Function in Heart Failure With Different Ejection Fraction Categories.

There are no studies of long-term worsening renal function (WRF) in heart failure (HF) with different ejection fraction (EF) groups. The aim was to compare incidence of, associations with and prognostic impact of WRF in HF with preserved (HFpEF), mid-range (HFmrEF), and reduced EF (HFrEF). The Swedish Heart Failure Registry (SwedeHF) was merged with the Stockholm Creatinine Measurement (SCREAM) registry 2006 to 2010. The associations between EF and WRF (≥25% decrease in eGFR) and the associations between WRF25-49% and WRF≥50% within year one and subsequent all-cause mortality were all assessed with multiadjusted Cox regression. Of 7,154 patients, 41.6% of HFpEF versus 34.5% and 35.4% of HFmrEF and HFrEF patients developed WRF≥25% during year one. The WRF risk was higher in HFpEF (reference) than in HFmrEF, hazard ratio (95% confidence interval) 0.890 (0.794 to 0.997) and HFrEF 0.870 (0.784 to 0.965). WRF within year one was strongly associated with subsequent long-term mortality in all EF groups, yielding adjusted HRs with WRF25-49% and WRF≥50%: HFpEF, 1.101 (0.913 to 1.328) and 2.096 (1.652 to 2.659), in HFmrEF 1.654 (1.353 to 2.022) and 2.375 (1.807 to 3.122) and in HFrEF 1.212 (1.060 to 1.386) and 1.694 (1.412 to 2.033). In conclusion, the long-term WRF risk was high in HF and highest in HFpEF. WRF was strongly associated with mortality in all EF groups, although in HFpEF only with the most severe WRF.

Association Between Mineralocorticoid Receptor Antagonist Use and Outcome in Myocardial Infarction Patients With Heart Failure.

BACKGROUND: There are no studies of mineralocorticoid receptor antagonist (MRA) treatment examining outcome in unselected real-life patients with myocardial infarction (MI) and heart failure (HF). There is uncertainty regarding effects of MRA in relation to left ventricular ejection fraction (LVEF) and chronic kidney disease (CKD). The aim was to assess MRA use and compare outcomes in MI patients with HF in relation to LVEF and CKD. METHODS AND RESULTS: Patients with MI and HF registered in the Swedish myocardial infarction registry, SWEDEHEART, 2005-2014, were included. Associations between MRA use and all-cause mortality up to 3 years were assessed with multivariable Cox regression, stratified by EF groups and presence of CKD (estimated glomerular filtration rate <60 mL/min per 1.73 m2). Of 45 071 patients with MI and HF, 4470 (9.9%) received MRA. Those with HF and LVEF <40% more often had MRA (19.6%) compared with those with LVEF 40% to 49% (9.1%) or LVEF ≥50% (4.7%). 8.6% of patients with CKD received MRA. After adjustment, MRA use was associated with lower mortality in those with LVEF <40% (hazard ratio [95% confidence interval] 0.81 [0.75-0.88]) and LVEF 40% to 49% (0.88 [0.75-1.03]) but not in those with LVEF ≥50% (1.29 [1.09-1.53]), with significant interaction between MRA and LVEF (P<0.0001). The association between MRA use and mortality was similar in those without (0.96 [0.88-1.05]) and with (0.92 [0.85-0.99]) CKD. CONCLUSIONS: In patients with MI and HF, MRA use was associated with better long-term survival in patients with LVEF <40% but not in those with LVEF ≥50%, while the mortality risk was similar in MRA-treated patients with or without CKD.

Haemodynamic effects of levosimendan in advanced but stable chronic heart failure.

AIMS: Levosimendan improves haemodynamics in acute decompensated heart failure (HF). However, it is increasingly used for repetitive or intermittent infusions in advanced but stable chronic HF, without clear indication, selection criteria, or effect. We tested the hypotheses that (1) levosimendan improves haemodynamics in stable chronic HF and (2) that the response is dependent on baseline clinical and haemodynamic factors. METHODS AND RESULTS: Twenty-three patients [median age 56 (49-64) years, four (17%) women] with stable New York Heart Association (NYHA) III and IV HF received a single 24 h levosimendan infusion. Non-invasive haemodynamics (inert gas re-breathing technique), estimated glomerular filtration rate, and N-terminal pro-brain natriuretic peptide were assessed before and after infusion. Levosimendan had the following effects (median change): a significant increase in cardiac output (+9.8 ± 21.6%; P = 0.026) and decrease in N-terminal pro-brain natriuretic peptide (-28.1 ± 16.3%, P < 0.001), estimated total peripheral resistance (-16.9 ± 18.3%, P = 0.005), and mean arterial pressure (-5.9 ± 8.2%, P = 0.007), but no change in estimated glomerular filtration rate (+0.89 ± 14.0%, P = 0.955). There were no significant associations between baseline clinical and/or haemodynamic factors and the levosimendan effect on cardiac output. CONCLUSIONS: Levosimendan was associated with improved haemodynamics in patients with stable chronic HF, but we could not identify any predictors of the magnitude of haemodynamic response.

Repetitive use of levosimendan in advanced heart failure: need for stronger evidence in a field in dire need of a useful therapy.

Patients in the latest stages of heart failure are severely compromised, with poor quality of life and frequent hospitalizations. Heart transplantation and left ventricular assist device implantation are viable options only for a minority, and intermittent or continuous infusions of positive inotropes may be needed as a bridge therapy or as a symptomatic approach. In these settings, levosimendan has potential advantages over conventional inotropes (catecholamines and phosphodiesterase inhibitors), such as sustained effects after initial infusion, synergy with beta-blockers, and no increase in oxygen consumption. Levosimendan has been suggested as a treatment that reduces re-hospitalization and improves quality of life. However, previous clinical studies of intermittent infusions of levosimendan were not powered to show statistical significance on key outcome parameters. A panel of 45 expert clinicians from 12 European countries met in Rome on November 24-25, 2016 to review the literature and envision an appropriately designed clinical trial addressing these needs. In the earlier FIGHT trial (daily subcutaneous injection of liraglutide in heart failure patients with reduced ejection fraction) a composite Global Rank Score was used as primary end-point where death, re-hospitalization, and change in N-terminal-prohormone-brain natriuretic peptide level were considered in a hierarchical order. In the present study, we tested the same end-point post hoc in the PERSIST and LEVOREP trials on oral and repeated i.v. levosimendan, respectively, and demonstrated superiority of levosimendan treatment vs placebo. The use of the same composite end-point in a properly powered study on repetitive levosimendan in advanced heart failure is strongly advocated.

Associations with and prognostic impact of chronic kidney disease in heart failure with preserved, mid-range, and reduced ejection fraction.

AIMS: As the role of chronic kidney disease (CKD) in different types of heart failure (HF) is poorly understood, our aim was to compare CKD in HF with preserved (HFpEF), mid-range (HFmrEF), and reduced ejection fraction (HFrEF) with regard to prevalence, associations and prognostic role. METHODS AND RESULTS: Patients in the Swedish Heart Failure Registry were divided into three groups based on EF (≥50%, 40-49% and <40%). CKD was defined as an estimated glomerular filtration rate ≤60 mL/min.1.73 m2 . Associations between covariates and CKD and between CKD and mortality were assessed with multivariable regressions. Of 40 230 patients, 8875 (22%) had HFpEF, 8374 (21%) had HFmrEF, and 22 981 (57%) had HFrEF, with a CKD prevalence of 56%, 48%, and 45%, respectively. Associations between covariates and CKD were similar in all EF groups. One-year mortality with vs. without CKD was 23% vs. 13% in HFpEF, 22% vs. 8% in HFmrEF, and 23% vs. 8% in HFrEF (P < 0.001 for all). After adjustment, CKD was more strongly associated with death in HFrEF and HFmrEF than in HFpEF [hazard ratio (HR) and 95% confidence interval (CI); 1.49 (1.42-1.56) and 1.51 (1.40-1.63) vs. 1.32 (1.24-1.42); P for interaction <0.001]. In receiver operating characteristic (ROC) analyses, CKD was also a stronger predictor of death in HFrEF and HFmrEF than in HFpEF [area under the curve (AUC) 0.699 (0.689-0.709) and 0.700 (0.683-0.716) vs. 0.629 (0.613-0.645)]. CONCLUSION: CKD was associated with similar covariates regardless of EF. Although CKD was more common in HFpEF than in HFmrEF and HFrEF, it may have more of a 'bystander' role in HFpEF, being less associated with mortality and with lower prognostic discrimination.

Prevalence and prognostic impact of kidney disease on heart failure patients.

OBJECTIVES: The aim was to determine the prevalence of different degrees of kidney dysfunction and to examine their association with short-term and long-term outcomes in a large unselected contemporary heart failure population and some of its subgroups. We examined to what extent the different cardiac conditions and their severity contribute to the prognostic value of kidney dysfunction in heart failure. DESIGN: We studied 47 716 patients in the Swedish Heart Failure Registry. Patients were divided into five renal function strata based on estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration equation. The adjusted association between kidney function and outcome was examined by Cox regression. RESULTS: 51% of the patients had eGFR <60 mL/min/1.73 m(2) and 11% had eGFR <30. There was increasing mortality with decreasing kidney function regardless of age, presence of diabetes, New York Heart Association NYHA class, duration of heart failure and haemoglobin levels. The risk HR (95% CI) persisted after adjusting for differences in baseline characteristics, severity of heart disease, and medical treatment: eGFR 60-89: 0.86 (0.79 to 0.95); eGFR 30-59: 1.13 (1.03 to 1.24); eGFR 15-29: 1.85 (1.67 to 2.07); and eGFR <15: 2.96 ([2.53 to -3.47)], compared with eGFR ≥90. CONCLUSIONS: Kidney dysfunction is common and strongly associated with short-term and long-term outcomes in patients with heart failure. This strong association was evident in all age groups, regardless of NYHA class, duration of heart failure, haemoglobin level, and presence/absence of diabetes mellitus. After adjusting for differences in baseline data, aetiology and severity of heart disease and treatment, the strong association remained.

Incidence, temporal trends, and prognostic impact of heart failure complicating acute myocardial infarction. The SWEDEHEART Registry (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies): a study of 199,851 patients admitted with index acute myocardial infarctions, 1996 to 2008.

OBJECTIVES: The aim of this study was to examine temporal trends in the incidence and outcomes of heart failure (HF) complicating acute myocardial infarction (AMI) in a large national cohort. BACKGROUND: There are limited and conflicting data concerning temporal trends in the incidence and prognostic implication of in-hospital HF that complicates AMI. METHODS: The nationwide coronary care unit registry SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) records baseline characteristics, treatments, and outcome of consecutive patients with AMIs admitted to all hospitals in Sweden. The diagnosis of HF requires the presence of crackles (Killip class ≥II) or the use of intravenous diuretic agents or intravenous inotropes. This study included 199,851 patients admitted for index AMIs between 1996 and 2008. RESULTS: The incidence of HF declined from 46% to 28% (p < 0.001). This decrease was more pronounced in patients with ST-segment elevation myocardial infarctions and left bundle branch block (from 50% to 28%) compared with those with non-ST-segment elevation myocardial infarctions (from 42% to 28%) (p < 0.001). The in-hospital, 30-day, and 1-year mortality rates for patients who developed HF during the index myocardial infarction decreased over the years from 19% to 13%, from 23% to 17%, and from 36% to 31%, respectively (p < 0.001 for all). Thirteen-year survival analysis showed higher mortality in patients with HF compared with those without HF (adjusted hazard ratio: 2.1; 95% confidence interval: 2.06 to 2.13). CONCLUSIONS: A marked decrease was found in the incidence of HF complicating AMI between 1996 and 2008. However, HF continues to worsen the early-, intermediate-, and long-term adverse prognostic risk after AMI.

Association between cardiovascular vs. non-cardiovascular co-morbidities and outcomes in heart failure with preserved ejection fraction.

AIMS: The prevalence of cardiovascular and non-cardiovascular co-morbidities and their relative importance for outcomes in heart failure with preserved ejection fraction (HFPEF) remain poorly characterized. This study aimed to investigate this. METHODS AND RESULTS: The Karolinska-Rennes (KaRen) Study was a multinational prospective observational study designed to characterize HFPEF. Inclusion required acute HF, defined by the Framingham criteria, LVEF ≥ 45%, and NT-pro-BNP ≥ 300 ng/L or BNP ≥ 100 ng/L. Detailed clinical data were collected at baseline and patients were followed prospectively for 18 months. Predictors of the primary (HF hospitalization or all-cause mortality) and secondary (all-cause mortality) outcomes were assessed with multivariable Cox regression. A total of 539 patients [56% women; median (interquartile range) age 79 (72-84) years; NT-pro-BNP/BNP 2448 (1290-4790)/429 (229-805) ng/L] were included. Known history of HF was present in 40%. Co-morbidities included hypertension (78%), atrial fibrillation/flutter (65%), anaemia (51%), renal dysfunction (46%), CAD (33%), diabetes (30%), lung disease (25%), and cancer (16%). The primary outcome occurred in 268 patients [50%; 106 deaths (20%) and 162 HF hospitalizations (30%)]. Important independent predictors of the primary and/or secondary outcomes were age, history of non-cardiovascular syncope, valve disease, anaemia, lower sodium, and higher potassium, but no cardiovascular co-morbidities. Renin-angiotensin system antagonist and mineralocorticoid receptor antagonist use predicted improved prognosis. CONCLUSION: HFPEF was associated with higher age, female gender, hypertension, atrial fibrillation/flutter, and numerous non-cardiovascular co-morbidities. Prognosis was determined by non-cardiovascular co-morbidities, but use of conventional heart failure medications may still be associated with improved outcomes.

Rationale and design of the Karolinska-Rennes (KaRen) prospective study of dyssynchrony in heart failure with preserved ejection fraction.

AIMS: Heart failure with preserved ejection fraction (HFPEF) is common but not well understood. Electrical dyssynchrony in systolic heart failure is harmful. Little is known about the prevalence and the prognostic impact of dyssynchrony in HFPEF. METHODS AND RESULTS: We have designed a prospective, multicenter, international, observational study to characterize HFPEF and to determine whether electrical or mechanical dyssynchrony affects prognosis. Patients presenting with acute heart failure (HF) will be screened so as to identify 400 patients with HFPEF. Inclusion criteria will be: acute presentation with Framingham criteria for HF, left ventricular ejection fraction>or=45%, brain natriuretic peptide (BNP)>100 pg/mL or NT-proBNP>300 pg/mL. Once stabilized, 4-8 weeks after the index presentation, patients will return and undergo questionnaires, serology, ECG, and Doppler echocardiography. Thereafter, patients will be followed for mortality and HF hospitalization every 6 months for at least 18 months. Sub-studies will focus on echocardiographic changes from the acute presentation to the stable condition and on exercise echocardiography, cardiopulmonary exercise testing, and serological markers. CONCLUSION: KaRen aims to characterize electrical and mechanical dyssynchrony and to assess its prognostic impact in HFPEF. The results might improve our understanding of HFPEF and generate answers to the question whether dyssynchrony could be a target for therapy in HFPEF.

Preserved microcirculatory response to acute estrogen not reflected by exercise capacity.

BACKGROUND: To assess the acute effect of a single dose of 10 mg oral micronized 17beta-estradiol on microcirculation in postmenopausal women with and without coronary artery disease and its potential influence on exercise capacity. METHODS: Postmenopausal women (n=11) with coronary artery disease had symptoms of ischemic heart disease and at least 1 mm ST depression at exercise. Microcirculation was examined by vital microscopy, with and without the acute administration of estrogen in a placebo-controlled cross-over design. Exercise test was performed on bicycle. The microcirculatory findings were contrasted to those in 14 healthy postmenopausal women. RESULTS: 17Beta-estradiol in serum and blood flow velocity increased significantly after acute oral estrogen administration both in women with coronary artery disease (p<0.001) and in healthy women (p<0.0001), with no significant difference between the two groups. No effect on exercise capacity or ST depression at exercise was detected. CONCLUSIONS: Previously reported data that a single dose of estrogen administered to postmenopausal women results in positive effects on exercise was not reproduced. An increased peripheral microvascular flow velocity was detected in women with coronary artery disease and this increase was not accompanied by an increased exercise capacity.