A case series of skin manifestations of infective endocarditis in contemporary era: just another book finding or a useful clinical sign?

BACKGROUND: Infective endocarditis (IE) is a disease of high morbidity and mortality. Infective endocarditis rarely involves skin manifestations in the contemporary era. The identification of typical skin lesions could be helpful in establishing early diagnosis of IE. CASE SUMMARY: We present four cases of IE hospitalized in our institution within a 12-month period. All patients were young and had skin manifestations on initial presentation (petechiae, splinter haemorrhages, Janeway lesions, and Osler's nodes), which led to a high clinical suspicion of IE confirmed by echocardiography and positive blood cultures. All cases had a complicated course. One patient died and the other three had prolonged hospital stay due to variable complications. DISCUSSION: Clinicians should always assess for skin manifestations in patients with fever especially when suspicion of IE is high. Occurrence of skin lesions in the course of IE may be associated with higher rate of complications and worse prognosis.

A tricky case of cardiogenic shock: Diagnostic challenges in the COVID-19 era.

Myocardial wall rupture should be considered in patients presenting with hypotension and STEMI especially of delayed onset. Diagnosing this entity in the COVID-19 era can be challenging-handheld echocardiography may aid toward this end.

Increased expression of blood muscarinic receptors in patients with reflex syncope.

AIMS: Pathophysiology of reflex syncope is not fully understood but a vagal overactivity might be involved in this syncope. Previously, overexpression of muscarinic M2 receptors and acetylcholinesterase was found in particular in the heart and in lymphocytes of rabbits with vagal overactivity as well as in hearts of Sudden Infant Death Syndromes. The aim of this present study was to look at M2 receptor expression in blood of patients with reflex syncope. The second objective was to measure acetylcholinesterase expression in these patients. METHODS AND RESULTS: 136 subjects were enrolled. This monocenter study pooled 45 adults exhibiting recurrent reflex syncope compared with 32 healthy adult volunteers (18-50 years) and 38 children exhibiting reflex syncope requiring hospitalization compared with 21 controls (1-17 years). One blood sample was taken from each subject and blood mRNA expression of M2 receptors was assessed by qRT-PCR. Taking into account the non-symmetric distributions of values in both groups, statistical interferences were assessed using bayesian techniques. A M2 receptor overexpression was observed in adult and pediatric patients compared to controls. The medians [q1;q3] were 0.9 [0.3;1.9] in patients versus 0.2 [0.1;1.0] in controls; the probability that M2 receptor expression was higher in patients than in controls (Pr[patients>controls]) was estimated at 0.99. Acetylcholinesterase expression was also increased 0.7 [0.4;1.6] in patients versus 0.4 [0.2;1.1] in controls; the probability that acetylcholinesterase expression was higher in patients than in controls (Pr[patients>controls]) was estimated at 0.97. Both in adults and children, the expression ratio of M2 receptors over acetylcholinesterase was greater in the patient group compared with the control group. CONCLUSION: M2 receptor overexpression has been detected in the blood of both, adults and children, exhibiting reflex syncope. As in our experimental model, i.e. rabbits with vagal overactivity, acetylcholinesterase overexpression was associated with M2 receptor overexpression. For the first time, biological abnormalities are identified in vagal syncope in which only clinical signs are, so far, taken into account for differential diagnosis and therapeutic management. Further work will be needed to validate potential biomarkers of risk or severity associated with the cholinergic system.

Diabetes Worsens Skeletal Muscle Mitochondrial Function, Oxidative Stress, and Apoptosis After Lower-Limb Ischemia-Reperfusion: Implication of the RISK and SAFE Pathways?

Objectives: Diabetic patients respond poorly to revascularization for peripheral arterial disease (PAD) but the underlying mechanisms are not well understood. We aimed to determine whether diabetes worsens ischemia-reperfusion (IR)-induced muscle dysfunction and the involvement of endogenous protective kinases in this process. Materials and Methods: Streptozotocin-induced diabetic and non-diabetic rats were randomized to control or to IR injury (3 h of aortic cross-clamping and 2 h of reperfusion). Mitochondrial respiration, reactive oxygen species (ROS) production, protein levels of superoxide dismutase (SOD2) and endogenous protective kinases (RISK and SAFE pathways) were investigated in rat gastrocnemius, together with upstream (GSK-3ß) and downstream (cleaved caspase-3) effectors of apoptosis. Results: Although already impaired when compared to non-diabetic controls at baseline, the decline in mitochondrial respiration after IR was more severe in diabetic rats. In diabetic animals, IR-triggered oxidative stress (increased ROS production and reduced SOD2 levels) and effectors of apoptosis (reduced GSK-3ß inactivation and higher cleaved caspase-3 levels) were increased to a higher level than in the non-diabetics. IR had no effect on the RISK pathway in non-diabetics and diabetic rats, but increased STAT 3 only in the latter. Conclusion: Type 1 diabetes worsens IR-induced skeletal muscle injury, endogenous protective pathways not being efficiently stimulated.

Similar clinical benefits from below-target and target dose enalapril in patients with heart failure in the SOLVD Treatment trial.

AIMS: To examine associations of below-target and target dose of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, with outcomes in patients with heart failure and reduced ejection fraction (HFrEF) in the Studies of Left Ventricular Dysfunction (SOLVD) Treatment trial. METHODS AND RESULTS: Two thousand five hundred and sixty-nine patients with HFrEF (ejection fraction ≤35%) were randomized to below-target (5-10 mg/day) dose placebo (n = 1284) or enalapril (n = 1285). One month post-randomization, blind up-titration to target (20 mg/day) dose was attempted for both study drugs in 2458 patients. Among the 1444 patients who achieved dose up-titration (placebo, n = 748; enalapril, n = 696; mean dose for both groups, 20.0 mg/day), target dose enalapril (vs. target dose placebo) was associated with a 9% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality [adjusted hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.60-0.81; P < 0.001] during 4 years of follow-up. Among the 1014 patients who could not achieve target dose (placebo, n = 486; enalapril, n = 528; mean dose for both groups, 8.8 mg/day), below-target dose enalapril (vs. below-target dose placebo) was associated with a 12% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 0.68; 95% CI 0.57-0.81; P < 0.001). Among the 1224 patients receiving enalapril, target (vs. below-target) dose had no association with the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 1.04; 95% CI 0.87-1.23; P = 0.695). CONCLUSION: In patients with HFrEF, the clinical benefits of ACE inhibitors appear to be similar at both below-target and target doses.

Impact of atrial fibrillation and heart failure, independent of each other and in combination, on mortality in community-dwelling older adults.

Atrial fibrillation (AF) and heart failure (HF), common in older adults, are associated with poor outcomes. However, little is known about their impact, independent of each other. We studied 5,673 community-dwelling adults aged ≥ 65 years in the Cardiovascular Health Study. Baseline prevalent AF and HF were centrally adjudicated, and 116 patients had AF only, 219 had HF only, 39 had both, and 5,263 had neither. The Cox proportional hazards model was used to estimate age-gender-race-adjusted hazard ratio (aHR) and 95% confidence intervals (CIs) for all-cause, cardiovascular (CV), and non-CV mortalities. Participants had a mean age of 73 years (± 6 years), 58% were women, and 15% African-American. During 13 years of follow-up, all-cause mortality occurred in 43%, 66%, 74%, and 85% of those with neither, AF only, HF only, and both, respectively. Compared with neither, aHR (95% CIs) for all-cause mortality associated with AF only, HF only, and both was 1.36 (1.08 to 1.72), 2.31 (1.97 to 2.71), and 3.04 (2.15 to 4.29), respectively. Similar associations were observed with CV mortality, but HF only also had greater non-CV mortality (aHR 1.72, 95% CI 1.35 to 2.18). Compared with AF alone, aHR (95% CIs) associated with HF alone for all-cause, CV, and non-CV mortalities was 1.69 (1.29 to 2.23), 1.73 (1.20 to 2.51), and 1.64 (1.09 to 2.46), respectively. Compared with HF alone, those with both conditions had greater CV but not all-cause mortality. In conclusion, community-dwelling older adults with AF have greater mortality than those without but lesser than those with HF, and both conditions were associated with greater CV and all-cause mortalities, whereas only those with HF had greater non-CV mortality.

Features of cardiac remodeling, associated with blood pressure and fibrosis biomarkers, are frequent in subjects with abdominal obesity.

Incidence and prevalence of abdominal obesity (AO) are growing exponentially. Subjects with AO are at higher risk of developing heart failure. The purpose of the study was to investigate early changes in cardiac and arterial structure and function and extracellular matrix biomarkers in normotensive healthy subjects with AO. Subjects with AO and age- and sex-matched controls underwent echocardiography, MRI (cardiac remodeling index), carotid intima-media thickness, pulse wave velocity, and blood fibrosis biomarkers measurements. We enrolled 87 subjects with AO and 53 controls. Although normotensive, subjects with AO had higher systolic blood pressure (BP; 122±11 versus 116±11 mm Hg; P=0.003), left ventricular mass (94±24 versus 84±21 g; P=0.034), and cardiac remodeling index (0.67±0.16 versus 0.60±0.10 g/mL; P=0.026) but unchanged carotid intima-media thickness and pulse wave velocity. Diastolic dysfunction (E' <10 cm/s) could be detected in 38% of subjects with AO (4% in controls). Left ventricular remodeling, as assessed by cardiac remodeling index, was positively and independently associated with higher BP (systolic BP and mean arterial pressure but not diastolic BP) and AO. Higher BP, AO, and procollagen-III-N-terminal peptide (≥2.4 ng/mL) concentrations (odds ratio, 4.15 [1.42-12.2]; P=0.01) were positively associated with diastolic dysfunction. Early cardiac structural remodeling, fibrosis, and diastolic dysfunction were detectable in healthy subjects with AO. Higher BP, procollagen-III-N-terminal peptide, and AO were independently associated with early cardiac structural and functional changes. It is to be investigated whether in subjects with AO, an early BP reduction, even if normotensive, combined with weight loss may avoid adverse cardiac remodeling and protect against progression to heart failure.

Three-dimensional imaging of pannus overgrowth after mitral valve repair.

We present the case of a 65-year-old man who was diagnosed with late mitral stenosis caused by pannus formation after Duran ring annuloplasty due to ischemicmitral regurgitation. Threedimensional echocardiography provided signifi cant information regarding the anatomy of the valve and the estimation of the severity of mitral stenosis.

Right ventricular ejection fraction <20% is an independent predictor of mortality but not of hospitalization in older systolic heart failure patients.

BACKGROUND: Reduced right ventricular ejection fraction (RVEF) is associated with poor outcomes in patients with chronic systolic heart failure (HF). Although most HF patients are older adults, little is known about the relationship between low RVEF and outcomes in older adults with systolic HF. METHODS: Of the 2008 Beta-Blocker Evaluation of Survival Trial (BEST) participants with systolic HF (left ventricular ejection fraction ≤ 35%) 822 were ≥ 65 years and had data on baseline RVEF estimated by gated-equilibrium radionuclide ventriculography. Using RVEF ≥ 40% (n = 308) as reference, we examined association of RVEF 30-39% (n = 214), 20-29% (n = 206) and <20% (n = 94) with outcomes using Cox regression models. RESULTS: All-cause mortality occurred in 36%, 40%, 39% and 56% of patients with RVEF ≥ 40%, 30-39%, 20-29% and <20% respectively. Compared with RVEF ≥ 40%, unadjusted hazard ratios (HR) and 95% confidence intervals (CI) for all-cause mortality associated with RVEF 30-39%, 20-29% and <20% were 1.19 (0.90-1.57; P = 0.220), 1.13 (0.84-1.51; P = 0.423) and 1.97 (1.43-2.73; P<0.001) respectively. Respective multivariable-adjusted HR's (95% CI's) for all-cause mortality were 1.19 (0.88-1.60; P = 0.261), 1.00 (0.73-1.39; P = 0.982) and 1.70 (1.14-2.53; P = 0.009). Adjusted HR's (95% CI's) associated with RVEF <20% (versus ≥ 40%) for cardiovascular mortality and HF mortality were 1.79 (1.17-2.76; P = 0.008) and 1.97 (1.02-3.83; P = 0.045) respectively. RVEF had no independent association with sudden cardiac death, all-cause or HF hospitalization. CONCLUSIONS: Abnormally low RVEF is a significant independent predictor of mortality, but not of HF hospitalization, in older adults with systolic HF.

Absence of obesity paradox in patients with chronic heart failure and diabetes mellitus: a propensity-matched study.

AIMS: Obesity is paradoxically associated with survival benefit in patients with chronic heart failure (HF). However, obesity complicates the management of diabetes mellitus (DM), which is common in HF. Yet, little is known about the impact of obesity in HF patients with DM. Therefore, we examined the association between obesity and outcomes in propensity-matched cohorts of HF patient with and without DM. METHODS AND RESULTS: Of the 7788 participants with chronic mild to moderate HF in the Digitalis Investigation Group trial, 7379 were non-cachectic [body mass index (BMI) ≥ 20 kg/m²] at baseline. Of these, 2153 (29%) had DM, of whom 798 (37%) were obese (BMI ≥ 30 kg/m²). Of the 5226 patients without DM, 1162 (22%) were obese. Propensity scores for obesity were used to separately assemble 636 pairs of obese and non-obese patients with DM and 770 pairs of obese and non-obese patients without DM, who were balanced on 32 baseline characteristics. Among matched patients with DM, all-cause mortality occurred in 38 and 39% of obese and non-obese patients, respectively [hazard ratio (HR) when obesity was compared with no obesity 0.99; 95% confidence interval (CI) 0.80-1.22; P = 0.915]. Among matched patients without DM, all-cause mortality occurred in 23 and 27% obese and non-obese patients, respectively (HR associated with obesity 0.77; 95% CI 0.61-0.97; P = 0.025). CONCLUSION: In patients with chronic mild to moderate HF and DM, obesity confers no paradoxical survival benefit. Whether intentional weight loss may improve outcomes in these patients needs to be investigated in future prospective studies.

Relationship between left and right ventricular ejection fractions in chronic advanced systolic heart failure: insights from the BEST trial.

AIMS: Abnormally low right ventricular ejection fraction (RVEF) is a predictor of poor outcomes in chronic heart failure (HF) patients with low left ventricular ejection fraction (LVEF). However, little is known about the relationship between LVEF and RVEF in these patients. METHODS AND RESULTS: Of the 2707 Beta-blocker Evaluation of Survival Trial (BEST) participants with ambulatory chronic HF, New York Heart Association class III-IV symptoms, and LVEF ≤ 35%, 2008 patients had gated-equilibrium radionuclide angiographic data on baseline LVEF and RVEF. Patients were categorized into quartiles by LVEF ≥ 29% (n = 507), 23-28% (n = 513), 17-22% (n = 538), and < 17% (n = 450). Logistic regression models were used to determine the association of LVEF quartiles (reference, ≥ 29%) with abnormally low RVEF (<20%). The prevalence of RVEF < 20% for patients with LVEF quartiles ≥ 29, 23-28, 17-22, and < 17% were 3, 6, 15, and 32%, respectively. Unadjusted odds ratios [95% confidence intervals (CIs)] for RVEF < 20% (vs. ≥ 20%) associated with LVEF quartiles 23-28, 17-22, and < 17% (reference, ≥ 29%) were 2.18 (1.14-4.17; P = 0.018), 6.32 (3.54-11.30; P < 0.001), and 16.67 (9.46-29.39; P < 0.001), respectively. Respective multivariable-adjusted odds ratios (95% CIs) were 1.82 (0.94-3.54; P = 0.076), 4.55 (2.48-8.35; P < 0.001), and 10.53 (5.70-19.44; P< 0.001), respectively. Heart failure symptoms and signs had unadjusted associations with low RVEF, but lacked intrinsic associations. CONCLUSION: In patients with advanced systolic HF, LVEF has a strong dose-dependent relationship with RVEF which is independent of other characteristics, and low LVEF is useful as a surrogate marker of abnormally low RVEF in these patients.

Oral potassium supplement use and outcomes in chronic heart failure: a propensity-matched study.

BACKGROUND: Hypokalemia is common in heart failure (HF) and is associated with increased mortality. Potassium supplements are commonly used to treat hypokalemia and maintain normokalemia. However, their long-term effects on outcomes in chronic HF are unknown. We used a public-use copy of the Digitalis Investigation Group (DIG) trial dataset to determine the associations of potassium supplement use with outcomes using a propensity-matched design. METHODS: Of the 7788 DIG participants with chronic HF, 2199 were using oral potassium supplements at baseline. We estimated propensity scores for potassium supplement use for each patient and used them to match 2131 pairs of patients receiving and not receiving potassium supplements. Matched Cox regression models were used to estimate associations of potassium supplement use with mortality and hospitalization during 40 months of median follow-up. RESULTS: All-cause mortality occurred in 818 (rate, 1327/10,000 person-years) and 802 (rate, 1313/10,000 person-years) patients respectively receiving and not receiving potassium supplements (hazard ratio {HR} when potassium supplement use was compared with nonuse, 1.05; 95% confidence interval {CI}, 0.94-1.18; P=0.390). All-cause hospitalizations occurred in 1516 (rate, 4777/10,000 person-years) and 1445 (rate, 4120/10,000 person-years) patients respectively receiving and not receiving potassium supplements (HR, 1.15; 95% CI, 1.05-1.26; P=0.004). HRs (95% CI) for hospitalizations due to cardiovascular causes and worsening HF were respectively 1.19 (95% CI, 1.08-1.32; P=0.001) and 1.27 (1.12-1.43; P<0.0001). CONCLUSION: The use of potassium supplements in chronic HF was not associated with mortality. However, their use was associated with increased hospitalization due to cardiovascular causes and progressive HF.

Timing of eplerenone initiation and outcomes in patients with heart failure after acute myocardial infarction complicated by left ventricular systolic dysfunction: insights from the EPHESUS trial.

AIMS: To test the hypothesis that an earlier post-acute myocardial infarction (AMI) eplerenone initiation in patients with left ventricular systolic dysfunction (LVSD) and heart failure (HF) is associated with better long-term outcomes. METHODS AND RESULTS: The 6632 patients of the EPHESUS study were randomized from day 3 to 14 after the index AMI (median = 7 days), of these 3319 were assigned to eplerenone. We analysed the differential effects of time-to-eplerenone initiation vs. placebo, based on the median time to initiation of treatment (<7 days-'earlier', > or =7days-'later'). Effects on outcomes were evaluated over a mean 16-month follow-up, using Cox proportional hazards regression analysis. The earlier eplerenone initiation (<7 days) reduced the risk of all-cause mortality by 31% (P = 0.001) when compared with the 'earlier' placebo' and also reduced the risks of cardiovascular (CV) hospitalization/CV mortality by 24% (P < 0.0001) and sudden cardiac death (SCD) by 34% (P < 0.0001). In contrast, later eplerenone initiation (> or =7 days) had no significant effect on outcomes. Interactions between time-to-randomization and treatment were significant. These associations remained substantially unchanged after risk adjustment in multivariable models. CONCLUSION: An earlier eplerenone administration (3-7days) post-AMI improved outcomes in patients with LVSD and HF. This benefit was not observed when eplerenone was initiated later (> or =7days).

A propensity-matched study of elevated jugular venous pressure and outcomes in chronic heart failure.

The independence of association between elevated jugular venous pressure (JVP) and outcomes in heart failure (HF) has not been well studied. The objective of propensity-matched study was to determine if an elevated JVP had intrinsic associations with outcomes in chronic systolic and diastolic HF. Of the 7,788 participants in the Digitalis Investigation Group trial, 1,020 (13%) had elevated JVP at baseline. Propensity scores for elevated JVP were estimated for all patients based on 32 baseline characteristics and were used to match 827 pairs of patients with normal and elevated JVP. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated to compare outcomes associated with elevated versus normal JVP during 34 months of median follow-up. Before matching, all-cause mortality occurred in 31% and 47% (unadjusted HR 1.70, 95% CI 1.54 to 1.88, p <0.0001), and all-cause hospitalization occurred in 60% and 71% (unadjusted HR 1.35, 95% CI 1.25 to 1.47, p <0.0001) of patients with normal and elevated JVP, respectively. After matching, all-cause mortality occurred in 48% and 45% (matched HR 0.95, 95% CI 0.80 to 1.12, p = 0.521), and all-cause hospitalization occurred in 70% and 70% (matched HR 0.97, 95% CI 0.87 to 1.09, p = 0.613) of patients with normal and elevated JVP, respectively. Elevated JVP had no intrinsic associations with cardiovascular mortality (matched HR 0.93, 95% CI 0.77 to 1.12, p = 0.440) or hospitalization for HF (matched HR 0.94, 95% CI 0.78 to 1.14, p = 0.532). In conclusion, an elevated JVP is a marker of higher burden of sickness and poor outcomes. However, elevated JVP had no intrinsic association with mortality or hospitalization in chronic HF.

Low serum magnesium and cardiovascular mortality in chronic heart failure: a propensity-matched study.

BACKGROUND: Low serum magnesium levels may cause fatal ventricular arrhythmias. However, their long-term effects on mortality and morbidity in chronic heart failure patients are relatively unknown. METHODS: We studied 1569 chronic systolic and diastolic heart failure patients with normal sinus rhythm who participated in the Digitalis Investigation Group trial and had serum magnesium data available at one month. Of these, 741 patients had normal (>2 mEq/L) and 828 had low (< or =2 mEq/L) serum magnesium levels. Propensity scores for having low serum magnesium levels were calculated for each patient using a non-parsimonious multivariable logistic regression model, and were used to match 560 (76%) low-magnesium patients with 560 normal-magnesium patients. Effects of low-magnesium on mortality and hospitalization during a mean follow-up of 36 months were assessed using matched Cox regression analyses. RESULTS: All-cause mortality occurred in 156 (rate, 915/10,000 person-years) normal- magnesium and 171 (rate, 1034/10,000 person-years) low-magnesium patients, respectively, during 1704 and 1653 years of follow-up (hazard ratio, 1.23; 95% confidence interval, 0.97-1.57; p=0.089). Cardiovascular mortality occurred in 110 (rate, 646/10,000 person-years) normal-magnesium and 133 (rate, 805/10,000 person-years) low-magnesium patients (hazard ratio, 1.38, 95% confidence interval, 1.04-1.83, p=0.024). Hazard ratios and 95% confidence intervals for all-cause and cardiovascular hospitalizations were respectively 1.18 (0.99-1.42; p=0.068) and 1.14 (0.94-1.39; p=0.182). CONCLUSIONS: In a propensity-matched population of ambulatory chronic heart failure patients who were balanced in all measured baseline covariates, serum magnesium level 2 mEq/L or less was associated with increased cardiovascular mortality, but had no association with cardiovascular hospitalization.

A propensity-matched study of outcomes of chronic heart failure (HF) in younger and older adults.

The majority of heart failure (HF) patients are older adults and most HF-related adverse events occur in these patients. However, the independent association of age and outcomes in HF is not clearly determined. We categorized 7788 ambulatory HF patients who participated in the Digitalis Investigation Group (DIG) trial as younger (< 65 years) and older (> or = 65 years). Propensity scores for older age were calculated for each patient and used to match 2381 pairs of younger and older patients. The associations of older age with mortality and hospitalization during a median 40 months of follow-up were assessed using matched Cox regression models. All-cause mortality occurred in 877 older patients versus 688 younger patients (hazard ratio when older age was compared with younger age (HR)=1.26; 95% confidence interval (CI)=1.12-1.41; p<0.0001). Older patients, when compared with propensity-matched younger patients, also had significantly higher mortality rates due to cardiovascular causes (HR=1.14; 95% CI=1.00-1.30; p=0.044) and worsening heart failure causes (HR=1.32; 95% CI=1.07-1.62; p=0.009). No significant association was found between age and hospitalization due to all causes (HR=1.08; 95% CI=0.99-1.18; p=0.084) and cardiovascular causes (HR=1.03; 95% CI=0.93-1.13; p=0.622). However, hospitalization due to HF was significantly increased in older patients (HR=1.14; 95% CI=1.01-1.28; p=0.041). In ambulatory HF patients, older age although associated with increased mortality, was not associated with increased hospitalizations except for those due to worsening HF.

A propensity-matched study of hypertension and increased stroke-related hospitalization in chronic heart failure.

Hypertension is a risk factor for heart failure and stroke. However, the effect of hypertension on stroke in patients with heart failure has not been well studied. In the Digitalis Investigation Group trial, 3,674 (47%) of the 7,788 patients had a history of hypertension. Probability or propensity scores for a history of hypertension were calculated for each patient through use of a multivariable logistic regression model and were then used to match 2,386 pairs of patients with and without a history of hypertension. Kaplan-Meier and matched Cox regression analyses were used to estimate associations of a history of hypertension hospitalization for stroke during 37 months of median follow-up. After matching, patients without and with a history of hypertension had a mean systolic blood pressure of 127 mm Hg. Hospitalization for stroke occurred in 90 patients (rate, 129/10,000 person-years of follow-up) without a history of hypertension and 121 patients (rate, 178/10,000 person-years of follow-up) with a history of hypertension (hazard ratio when hypertension was compared with no hypertension=1.52; 95% confidence interval=1.11 to 2.08; p=0.010). This association was also observed among patients with baseline systolic blood pressure <140 mm Hg (hazard ratio=1.35; 95% confidence interval=1.01 to 1.81; p=0.044). In conclusion, a history of hypertension was associated with increased risk of hospitalization for stroke among patients with heart failure who were balanced in all measured baseline covariates, including blood pressure.

Ejection fraction and blood pressure are important and interactive predictors of 4-week mortality in severe acute heart failure.

BACKGROUND: In acute heart failure syndromes (AHFS), the prognostic value of left ventricular ejection fraction (LVEF), although widely accepted, has been recently challenged. In contrast, blood pressure is increasingly gaining ground over LVEF as predictor of mortality. Therefore, it is not clear whether both LVEF and mean arterial pressure (MAP) are independent risk factors in patients with AHFS. METHODS AND RESULTS: The EFICA study enrolled 581 AHFS patients admitted to 60 CCU/ICUs. Survival at 4 weeks was analyzed for all cases with echocardiographic LVEF available on admission (n=355). Four-week mortality was 23%. Multivariable analysis identified lower LVEF, lower MAP and serum creatinine >1.5 mg/dl as independent correlates of mortality (respectively, OR: 1.27 per 10% decrease, CI: 1.05-1.53, p=0.012; OR: 1.30 per 10 mmHg decrease, CI: 1.15-1.48, p<0.0001; OR: 2.84, CI: 1.64-4.93, p=0.0002). LVEF interacted significantly with MAP (p<0.0001) and the subgroup analysis showed that reduced LVEF was a strong risk factor in patients with MAP 90 mmHg. CONCLUSIONS: Both LVEF and MAP are important predictors of death in severe AHFS. LVEF can provide additional prognostic information on top of MAP but mainly in patients with low MAP (

The challenge of acute decompensated heart failure.

Acute heart failure syndromes (AHFS) is a broad spectrum of heterogeneous conditions including pulmonary oedema, hypertensive crisis, worsening exacerbated CHF and cardiogenic shock. HF hospitalizations have steadily risen with more than one million in 2004 in the United States and a similar number has been reported in Europe. Each year heart failure accounts for 6.5 million days spent in hospital in the USA and 1.4 million days in France. Mortality data are derived from registries or clinical trials. Registry data in patients admitted to general or cardiology wards such as in Euroheart Failure Survey and ADHERE provide a far more optimistic picture compared with data from consecutive unselected patients in the most acute situation. such as in EFICA. Four-week mortality was higher than 25% in this case. A great pathophysiologic understanding of the different features of the various AHFS is needed in order to identify targets for therapy and research. This includes hemodynamics, the role of myocardial injury, neurohormonal and cytokine abnormalities and the cardiorenal syndromes. So far, very little progress has been made in developing new, effective therapies and implementing management guidelines in this patient population. Future clinical trial endpoints should be better designed and tailored to the various pathophysiological conditions of this complex syndrome. The goal of AHFS therapy is not only to prevent disease progression but also to have a beneficial effect on an acute event that exacerbates disease progression. A combined endpoint assessing survival and rehospitalisation rates is becoming increasingly popular for acute therapies. Specific trials may also need to be designed according to the time of access to the patient.