Endpoint Of Heart Failure Research Articles

PTH, FGF23, and Intensive Blood Pressure Lowering in Chronic Kidney Disease Participants in SPRINT.

The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated that intensive BP lowering reduced the risk of cardiovascular disease, but increased eGFR decline. Serum parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23) concentrations are elevated in CKD and are associated with cardiovascular disease. We evaluated whether intact PTH or intact FGF23 concentrations modify the effects of intensive BP control on cardiovascular events, heart failure, and all-cause mortality in SPRINT participants with CKD. We measured PTH and FGF23 in 2486 SPRINT participants with eGFR<60 ml/min per 1.73 m2 at baseline. Cox models were used to evaluate whether serum PTH and FGF23 concentrations were associated with cardiovascular events, heart failure, and all-cause mortality, and whether PTH and FGF23 modified the effects of intensive BP control. The mean age of this subcohort was 73 years, 60% were men, and mean eGFR was 46±11 ml/min per 1.73 m2. Median PTH was 48 (interquartile range [IQR], 35-67) pg/ml and FGF23 was 66 (IQR, 52-88) pg/ml. There were 261 composite cardiovascular events, 102 heart failure events, and 179 deaths within the subcohort. The adjusted hazard ratio (HR) per doubling of PTH concentration for cardiovascular events, heart failure, and all-cause mortality were 1.29 (95% confidence interval [95% CI], 1.06 to 1.57), 1.32 (95% CI, 0.96 to 1.83), and 1.04 (95% CI, 0.82 to 1.31), respectively. There were significant interactions between PTH and BP arm for both the cardiovascular (P-interaction=0.01) and heart failure (P-interaction=0.004) end points. Participants with a PTH above the median experienced attenuated benefits of intensive BP control on cardiovascular events (adjusted HR, 1.02; 95% CI, 0.72 to 1.42) compared with participants with a PTH below the median (adjusted HR, 0.67; 95% CI, 0.45 to 1.00). FGF23 was not independently associated with any outcome and did not modify the effects of the intervention. SPRINT participants with CKD and a high serum PTH received less cardiovascular protection from intensive BP therapy than participants with a lower serum PTH.

Abstract 17186: Left Atrial Strain Predicts Adverse Outcomes in Hypertrophic Cardiomyopathy

Introduction: Hypertrophic cardiomyopathy (HCM) patients are at increased risk for heart failure (HF), stroke, death, and paroxysmal atrial fibrillation (PAF) development. There is no consensus whether atrial fibrillation (AF) is a marker or mediator of adverse outcomes in HCM patients. Hypothesis: We hypothesized that PAF and left atrial (LA) remodeling predict adverse outcomes in HCM. Methods: Echocardiography (2D and speckle tracking) was used to assess LA size, function, and mechanics in a cohort of HCM patients with history of PAF (PAF group, n=45) and age/gender-matched HCM patients without history of AF (No-AF group; n=59). AF was diagnosed by review of EKGs, event recorder/holter monitor data, and ICD interrogation. Patients were followed for a mean of 53 months for development of the composite endpoint of HF, death, and stroke. Results: Clinical/demographic characteristics were similar in the 2 groups; 67% of PAF group had a CHADS 2 VASC score ≤ 1. The PAF group had higher LA volume, lower LA ejection fraction, and higher E/A ratio (reflecting LV diastolic dysfunction) compared to the No-AF group. LA contractile and reservoir strain/strain rate (SR) were significantly lower in the PAF group (Table 1). Male gender, LA reservoir and conduit strain/SR (not PAF presence) were associated with the development of the composite endpoint in univariate analysis. Only LA conduit and reservoir strain/SR independently predicted the composite endpoint in a multivariate model. Kaplan Meier survival analysis showed greater event-free survival among HCM patients with LA conduit strain &gt;10.2% (Figure 1a) and LA reservoir strain &gt;23.8% (p &lt; 0.01) (Figure 1b). Conclusions: PAF is associated with greater degree of LA myopathy in HCM. LA myopathy assessed by conduit and reservoir strain/SR may be useful for risk stratification for HF, stroke, and death in HCM.

Association of myocardial fibrosis and cardiovascular events: the multi-ethnic study of atherosclerosis.

We used contrast-enhanced cardiac magnetic resonance (CMR) to evaluate differences in myocardial fibrosis measured at the year-10 examination between participants with and without cardiovascular (CV) events accrued in a large population based study over the preceding 10-year follow-up period in this retrospective study. The MESA study enrolled 6814 participants free of CV disease at baseline (2000-2002). We included MESA participants who underwent contrast-enhanced CMR at the MESA year-10 exam (N = 1840). We defined a composite CV endpoint of coronary heart disease, heart failure, atrial fibrillation, stroke, and peripheral artery disease. Using CMR, we characterized myocardial fibrosis with late-gadolinium enhancement for scar and T1 mapping indices of diffuse fibrosis. Demographic and CV-risk adjusted logistic (presence of scar) and linear regression (pre-contrast T1, T1 at 12 and 25 min post-contrast, and extracellular volume fraction or ECV) models were used to assess the relationship between fibrosis and events. The mean values of T1 indices were-pre-contrast T1: 977 ± 45 ms; T1 at 12': 456 ± 40 ms; T1 at 25': 519 ± 41 ms; ECV: 27.1 ± 3.2%. One-hundred and forty-six (7.9%) participants had myocardial scar. The presence of scar was strongly associated with prior CV events (adjusted coeff: 1.36, P < 0.001). Lower post-contrast T1 times and higher ECV, indicative of greater diffuse fibrosis were strongly associated with CV events (T1 at 12': coeff = -10.0 ms, P = 0.004; T1 at 25': coeff =-9.2 ms, P = 0.008; ECV: coeff = 1.31%, P < 0.001). Individuals who suffered prior CV events have greater likelihood of diffuse myocardial fibrosis when compared with event-free individuals living in the same community.

The stricter criteria for Class I CRT indication suggested by the 2016 ESC Guidelines reliably exclude patients with a worse prognosis in comparison with the 2013 ESC indication criteria

BackgroundThe European Society of Cardiology (ESC) Guidelines published in 2016 modified indications for cardiac resynchronization therapy (CRT) in comparison with the 2013 ESC Guidelines. The aim of this analysis was to evaluate the impact of the stricter criteria suggested by the 2016 ESC Guidelines on patient outcome in a real-world population. MethodsWe collected data on 930 consecutive patients with complete outcome information who had undergone CRT implantation from 2011 to 2013 from the CRT-MORE registry. Patients were classified according to 2013 (Reference) and 2016 (Current) ESC Guidelines. The primary end-point of the study was death from any cause and heart failure hospitalization. ResultsAccording to the Reference Guidelines, 650 (69.9%) patients met Class I indications, 190 (20.4%) Class IIa, 39 (4.2%) Class IIb and 51 (5.5%) Class III. According to the Current Guidelines, 563 (60.5%) patients met Class I indications, 145 (15.6%) Class IIa, 108 (11.6%) Class IIb and 114 (12.3%) Class III. On comparing the Reference and Current Guidelines, the 538 patients who confirmed their Class I indication had a better outcome in terms of freedom from the combined end-point of heart failure (HF) hospitalization or death from any cause (hazard ratio (HR) of 0.64; 95% CI 0.42 to 0.99; p = 0.0436) when compared to the 112 patients who lost their class I indication (84 moved to class IIb and 28 moved to class III). ConclusionsThe stricter criteria for Class I CRT indication suggested by the 2016 ESC Guidelines excluded about 20% of patients with a worse prognosis.Clinical Trial Registration: CRT MORE: Cardiac Resynchronization Therapy Modular Registry URL: http://clinicaltrials.gov/Identifier:NCT01573091.

Clinical and prognostic impact of chronotropic incompetence in patients with hypertrophic cardiomyopathy

BackgroundA blunted heart rate (HR) response is associated with an impaired peak oxygen uptake (pVO2), a powerful outcome predictor in hypertrophic cardiomyopathy (HCM). The present multicenter study sought to determine the prognostic role for exercise-induced HR response in HCM. MethodsA total of 681 consecutive HCM outpatients on optimized treatment were recruited. The heart failure (HF) end-point was death due to HF, cardiac transplantation, NYHA III-IV class progression, HF worsening leading to hospitalization and severe functional deterioration leading to septal reduction. The sudden cardiac death (SCD) end-point included SCD, aborted SCD and appropriate implantable cardioverter defibrillator discharges. ResultsDuring a median follow-up of 4.2 years (25–75th centile: 3.9–5.2), 81 patients reached the HF and 23 the SCD end-point. Covariates with independent effects on the HF end-point were left atrial diameter, left ventricular ejection fraction, maximal left ventricular outflow tract gradient and exercise cardiac power (ECP = pVO2∗systolic blood pressure) (C-Index = 0.807) whereas the HCM Risk-SCD score and the ECP remained associated with the SCD end-point (C-Index = 0.674). When the VO2-derived variables were not pursued, peak HR (pHR) re-entered in the multivariate HF model (C-Index = 0.777) and, marginally, in the SCD model (C-index = 0.656). A pHR = 70% of the maximum predicted resulted as the best cut-off value in predicting the HF-related events. ConclusionsThe cardiopulmonary exercise test is pivotal in the HCM management, however the pHR remains a meaningful alternative parameter. A pHR < 70% identified a HCM population at high risk of HF-related events, thus calling for a reappraisal of the chronotropic incompetence threshold in HCM.

Development of and Progression of Overt Heart Failure in Nonobstructive Hypertrophic Cardiomyopathy

Only few studies aimed at identifying predictors of heart failure (HF) in hypertrophic cardiomyopathy (HC) patients. Furthermore, serial echocardiographic analyses are lacking in these patients and little is known about the natural progression of left ventricular (LV) abnormalities and their association with HF development. Aim of this study was to assess the prognostic value of LV global longitudinal strain (GLS) and other clinical and echocardiographic characteristics for the development of HF in patients with nonobstructive HC; furthermore, changes in echocardiographic parameters over time were correlated with HF development. Echocardiography was performed in 236 HC patients (68% men, age: 50 ± 14 years) at their initial visit and during follow-up (6.5(4.1 to 9.8) years). The end point of new HF development or progression to New York Heart Association class III/IV was noted and echocardiographic changes over time were compared among patients with and without HF using linear mixed model analysis. In total, 40 patients reached the HF end point. Multivariable cox regression analysis showed that age (HR 1.04(1.01 to 1.06), p = 0.016), New York Heart Association class (HR 2.30(1.07 to 4.95), p = 0.033), GLS (HR 1.15(1.05 to 1.22), p = 0.001), and left atrial volume (LAVI, HR 2.22(1.10 to 4.50), p = 0.027) were independently associated with the HF end point. Echocardiographic parameters, including GLS and LAVI, remained stable over time in patients without HF end point, but changed significantly in patients who developed HF (group-time interaction, p = 0.042 for GLS and p = 0.027 for LAVI). In conclusion, LV dysfunction is a progressive phenomenon in nonobstructive HC patients which can be detected by repeated echocardiography. Importantly, GLS and LAVI at baseline as well as their changes over time are associated with HF.

Ventricular Electrical Delay Measured From Body Surface ECGs Is Associated With Cardiac Resynchronization Therapy Response in Left Bundle Branch Block Patients From the MADIT-CRT Trial (Multicenter Automatic Defibrillator Implantation-Cardiac Resynchronization Therapy).

Although cardiac resynchronization therapy (CRT) is beneficial in heart failure patients with left bundle branch block, 30% of these patients do not respond to the therapy. Identifying these patients before implantation of the device is one of the current challenges in clinical cardiology. We verified the diagnostic contribution and an optimized computerized approach to measuring ventricular electrical activation delay (VED) from body surface 12-lead ECGs. We applied the method to ECGs acquired before implantation (baseline) in the MADIT-CRT trial (Multicenter Automatic Defibrillator Implantation-Cardiac Resynchronization Therapy). VED values were dichotomized using its quartiles, and we tested the association of VED values with the MADIT-CRT primary end point of heart failure or death. Multivariate Cox proportional models were used to estimate the risk of study end points. In addition, the association between VED values and hemodynamic changes after CRT-D implantation was examined using 1-year follow-up echocardiograms. Our results showed that left bundle branch block patients with baseline VED <31.2 ms had a 35% risk of MADIT-CRT end points, whereas patients with VED ≥31.2 ms had a 14% risk (P<0.001). The hazard ratio for predicting primary end points in patients with low VED was 2.34 (95% confidence interval, 1.53-3.57; P<0.001). Higher VED values were also associated with beneficial hemodynamic changes. These strong VED associations were not found in the right bundle branch block and intraventricular conduction delay cohorts of the MADIT-CRT trial. Left bundle branch block patients with a high baseline VED value benefited most from CRT, whereas left bundle branch block patients with low VED did not show CRT benefits.

Long-term clinical outcomes of cardiac resynchronization therapy with or without defibrillation: impact of the aetiology of cardiomyopathy.

AimsThere is a continuing debate as to whether cardiac resynchronization therapy-defibrillation (CRT-D) is superior to CRT-pacing (CRT-P), particularly in patients with non-ischaemic cardiomyopathy (NICM). We sought to quantify the clinical outcomes after primary prevention of CRT-D and CRT-P and identify whether these differed according to the aetiology of cardiomyopathy.Methods and resultsAnalyses were undertaken in the total study population of patients treated with CRT-D (n = 551) or CRT-P (n = 999) and in propensity-matched samples. Device choice was governed by the clinical guidelines in the United Kingdom. In univariable analyses of the total study population, for a maximum follow-up of 16 years (median 4.7 years, interquartile range 2.4–7.1), CRT-D was associated with a lower total mortality [hazard ratio (HR) 0.72] and the composite endpoints of total mortality or heart failure (HF) hospitalization (HR 0.72) and total mortality or hospitalization for major adverse cardiac events (MACE; HR 0.71) (all P < 0.001). After propensity matching (n = 796), CRT-D was associated with a lower total mortality (HR 0.72) and the composite endpoints (all P < 0.01). When further stratified according to aetiology, CRT-D was associated with a lower total mortality (HR 0.62), total mortality or HF hospitalization (HR 0.63), and total mortality or hospitalization for MACE (HR 0.59) (all P < 0.001) in patients with ischaemic cardiomyopathy (ICM). There were no differences in outcomes between CRT-D and CRT-P in patients with NICM.ConclusionIn this study of real-world clinical practice, CRT-D was superior to CRT-P with respect to total mortality and composite endpoints, independent of known confounders. The benefit of CRT-D was evident in ICM but not in NICM.

Usefulness of the CHADS2 and R2CHADS2 scores for prognostic stratification in patients with coronary artery disease.

ObjectiveThe current risk model for long-term prediction in coronary artery disease (CAD) is complicated, while a simple useful model is still lacking. We aim to investigate if CHADS2 and R2CHADS2 scores could predict long-term outcome for patients with CAD.Patients and methodsWe enrolled 3,700 patients with CAD between November 2010 and September 2014 at the Department of Cardiology from Chinese PLA General Hospital. The CHADS2 and R2CHADS2 scores were calculated. All cases were followed to track the incidence of composite end point consisting of cardiovascular (CV) death, myocardial infarction (MI), stroke, heart failure, and all-cause death.ResultsDuring a median 2.9-year follow-up, 443 patients experienced at least one element of the composite end point of CV death (n=168 [4.6%]), MI (n=59 [1.6%]), stroke (n=96 [2.6%]), heart failure (n=101 [2.8%]), and all-cause death (n=240 [6.6%]). Multivariate Cox regression analyses showed that the CHADS2 score (hazard ratio [HR]: 2.18, 95% CI: 2.00–2.38, p<0.0001) and the R2CHADS2 score (HR: 1.93, 95% CI: 1.83–2.04, p<0.0001) were independently associated with composite outcome. Receiver-operating characteristic analysis showed that compared with the CHADS2 score, the R2CHADS2 score had better discrimination for the prediction of long-term combined outcome (0.772 vs 0.791, p=0.0013).ConclusionCHADS2 and R2CHADS2 scores provide a quick and useful tool in predicting long-term outcome for patients with CAD.

The beneficial effect of weight reduction on adverse cardiovascular outcomes following bariatric surgery is attenuated in patients with obstructive sleep apnea.

Weight loss after bariatric surgery is associated with reduction in adverse cardiovascular outcomes; however, the impact of obstructive sleep apnea (OSA) on reduction of cardiovascular outcomes after bariatric surgery in morbidly obese patients is not known. We retrospectively assessed differences in cardiovascular events after laparoscopic adjustable gastric banding (LAGB)-induced weight loss in patients with and without OSA before and after propensity score matching for age, sex, body mass index (BMI), and major comorbidities between the two groups and determined predictors of poor outcomes. OSA was present in 222 out of 830 patients (27 per cent) who underwent LAGB between 2001 and 2011. Despite a similar reduction in BMI (20.0 and 20.8 per cent), a significantly higher percentage of cardiovascular events were observed in patients with than without OSA (35.6 vs 6.9 per cent; p < 0.001) at 3 years (mean follow-up 6.0 ± 3.2; range: 0.5 to 13 years). The differences in the cumulative endpoint of new onset stroke, heart failure, myocardial infarction, venous thrombosis, and pulmonary embolism between the OSA and non-OSA groups were maintained after propensity matching. Patients with OSA treated with continuous positive airway pressure (CPAP) during sleep [n = 66] had lower cardiovascular event rates at 30 months compared with those not treated (p < 0.041). OSA (hazard ratio: 6.92, 95% CI: 3.39-14.13, p < 0.001) remained an independent predictor of cardiovascular events after multivariate analysis. Thus, patients with OSA, despite a similar initial weight loss after LAGB, had a higher incidence of cardiovascular events compared with a propensity-matched group without OSA. Treatment with CPAP appears to reduce such events.

Relationship between the serum level and its change of N-terminal pro-B-type natriuretic peptides and prognosis of acute decompensated heart failure with preserved ejection fraction in the elderly

Objective To assess the prognostic value of the serum level and its change of N-terminal pro-B-type natriuretic peptides (NT-proBNP) in the elderly with acute decompensated heart failure with preserved ejection fraction (HFpEF). Methods A total of 138 consecutive patients (≥65 years old) admitted in Geriatrics and Gerontology Department at Beijing Friendship Hospital were enrolled from June 2013 to June 2015.Demographic characteristics, combination of diseases, medication administration, laboratorial and echocardiographic data were recorded.Meanwhile, NT-proBNP levels at admission, 7th day after admission, changes over 7 days were also recorded and calculated.At the end of 1 year follow up, all patients were divided into events group (n=72) with, and control group (n=66) without, adverse outcomes of heart failure death, heart failure readmission and all-cause death.The differences in NT-proBNP level at admission, 7th day after admission, and its changed value and rate over 7 days were compared between the two groups.Logistic regression was used for analysis of independent risk factors for prognosis.And the cut-off points of NT-proBNP values to predict adverse events were determined by receiver operating characteristic(ROC)curve. Results NT-proBNP values were significantly higher at admission and at 7th days after admission in the events group than in control group(P=0.000). There were no significantly differences in NT-proBNP level and its changes over 7 days between two groups (P=0.370 and P=0.272). Logistic regression analysis showed that NT-proBNP values at admission and 7th days after admission, and NYHA functional classification were independent risk factors for adverse outcomes in 1 year in the elderly with HFpEF (all P<0.05). Furthermore, by the ROC curve, NT-proBNP values at admission and 7th days after admission could predict adverse outcomes including composite endpoints of heart failure, re-admission, heart failure associated death, and all-cause mortality in 1 year. Conclusions Both the plasma NT-proBNP levels at admission and at 7th days after admission have a correlation with prognosis in elderly patients with acute decompensated HFpEF, while changes of NT-proBNP concentration over 7 days could not predict adverse outcomes in this cohort. Key words: Stroke volume; Heart failure; Natriuretic peptide, brain

Identifying unmet clinical need in hypertrophic cardiomyopathy using national electronic health records.

IntroductionTo evaluate unmet clinical need in unselected hypertrophic cardiomyopathy (HCM) patients to determine the risk of a wide range of subsequent cardiovascular disease endpoints and safety endpoints relevant for trial design.MethodsPopulation based cohort (CALIBER, linked primary care, hospital and mortality records in England, period 1997–2010), all people diagnosed with HCM were identified and matched by age, sex and general practice with ten randomly selected people without HCM. Random-effects Poisson models were used to assess the associations between HCM and cardiovascular diseases and bleeding.ResultsAmong 3,290,455 eligible people a diagnosis of hypertrophic cardiomyopathy was found in 4 per 10,000. Forty-one percent of the 1,160 individuals with hypertrophic cardiomyopathy were women and the median age was 57 years. The median follow-up was 4.0 years. Compared to general population controls, people with HCM had higher risk of ventricular arrhythmia (incidence rate ratio = 23.53, [95% confidence interval 12.67–43.72]), cardiac arrest or sudden cardiac death (6.33 [3.69–10.85]), heart failure (4.31, [3.30–5.62]), and atrial fibrillation (3.80 [3.04–4.75]). HCM was also associated with a higher incidence of myocardial infarction ([MI] 1.90 [1.27–2.84]) and coronary revascularisation (2.32 [1.46–3.69]).The absolute Kaplan-Meier risks at 3 years were 8.8% for the composite endpoint of cardiovascular death or heart failure, 8.4% for the composite of cardiovascular death, stroke or myocardial infarction, and 1.5% for major bleeding.ConclusionsOur study identified major unmet need in HCM and highlighted the importance of implementing improved cardiovascular prevention strategies to increase life-expectancy of the contemporary HCM population. They also show that national electronic health records provide an effective method for identifying outcomes and clinically relevant estimates of composite efficacy and safety endpoints essential for trial design in rare diseases.

Electrocardiographic Predictors of Morbidity and Mortality in Patients With Acute Myocarditis: The Importance of QRS-T Angle

BackgroundAcute myocarditis carries a variable prognosis. We evaluated the morbidity and mortality rates in patients with acute myocarditis and admission electrocardiographic predictors of outcome. Methods and ResultsPatients admitted to a tertiary hospital with a clinical diagnosis of acute myocarditis were evaluated; 193 patients were included. Median follow-up was 5.7 years, 82% were male, and overal median age was 30 years (range 21–39). The most common clinical presentations were chest pain (77%) and fever (53%). The 30-day survival rate was 98.9%. Overall survival during follow-up was 94.3%. The most common abnormalities observed on electrocardiography were T-wave changes (36%) and ST-segment changes (32%). Less frequent changes included abnormal T-wave axis (>105° or < −15°; 16%), abnormal QRS axis (12%), QTc >460 ms (11%), and QRS interval ≥120 ms (5%). Wide QRS-T angle (≥100°) was demonstrated in 13% of the patients and was associated with an increased mortality rate compared with patients with a narrow QRS-T angle (20% vs 4%; P = .007). The rate of heart failure among patients with a wide QRS-T angle was significantly higher (36% vs 10%; P = .001). Cox regression analysis demonstrated that a wide QRS-T angle (≥100°) was a significant independent predictor of heart failure (hazard ratio [HR] 3.20, 95% confidence interval [CI] 1.35–7.59; P < .01) and of the combined end point of death or heart failure (HR 2.56, 95% CI 1.14–5.75; P < .05). ConclusionsQRS-T angle is a predictor of increased morbidity and mortality in acute myocarditis.

Sudden cardiac death and pump failure death prediction in chronic heart failure by combining ECG and clinical markers in an integrated risk model.

BackgroundSudden cardiac death (SCD) and pump failure death (PFD) are common endpoints in chronic heart failure (CHF) patients, but prevention strategies are different. Currently used tools to specifically predict these endpoints are limited. We developed risk models to specifically assess SCD and PFD risk in CHF by combining ECG markers and clinical variables.MethodsThe relation of clinical and ECG markers with SCD and PFD risk was assessed in 597 patients enrolled in the MUSIC (MUerte Súbita en Insuficiencia Cardiaca) study. ECG indices included: turbulence slope (TS), reflecting autonomic dysfunction; T-wave alternans (TWA), reflecting ventricular repolarization instability; and T-peak-to-end restitution (ΔαTpe) and T-wave morphology restitution (TMR), both reflecting changes in dispersion of repolarization due to heart rate changes. Standard clinical indices were also included.ResultsThe indices with the greatest SCD prognostic impact were gender, New York Heart Association (NYHA) class, left ventricular ejection fraction, TWA, ΔαTpe and TMR. For PFD, the indices were diabetes, NYHA class, ΔαTpe and TS. Using a model with only clinical variables, the hazard ratios (HRs) for SCD and PFD for patients in the high-risk group (fifth quintile of risk score) with respect to patients in the low-risk group (first and second quintiles of risk score) were both greater than 4. HRs for SCD and PFD increased to 9 and 11 when using a model including only ECG markers, and to 14 and 13, when combining clinical and ECG markers.ConclusionThe inclusion of ECG markers capturing complementary pro-arrhythmic and pump failure mechanisms into risk models based only on standard clinical variables substantially improves prediction of SCD and PFD in CHF patients.

Outcomes of acute kidney injury in a nephrology ward.

Acute kidney injury (AKI) is a global problem which predicts immediate and long-term adverse outcomes. We evaluated the AKI progression to end-stage renal disease, as well as the mortality associated with AKI and the in-hospital readmission rate because of a cardiovascular event in AKI patients admitted in a nephrology ward. A 5-year retrospective study was set in a nephrology department, with a follow-up period of up to 8years. In a total of 191 patients, mean age was 73.83±12.49years, and 137 (71.7%) patients had history of chronic kidney disease. One hundred and twenty-four (65%) patients needed RRT and two (1%) needed surgery. Upon discharge, 107 (56%) patients had recovered the renal function, 41 (21.6%) patients had partial recovery, 25 (13%) patients were RRT dependent, 16 (8.4%) died, and two (1%) patients had outcomes unknown to us, because they were transferred to other hospitals. The median survival time free of RRT was 74months. The median survival time of the followed patients was 34months (95% CI 23.3-44.7). The mortality rate in the follow-up period in this sample was 18 deaths/100 patients-years, and the incidence of a composite cardiovascular endpoint of heart failure, acute coronary syndrome, and stroke was 6 events/100 patients-years. The mortality rate in the follow-up period was higher than usually described for patients outside intensive care unit, probably because our patients were old and had many comorbidities.

Aldosterone, Renin, Cardiovascular Events, and All-Cause Mortality Among African Americans: The Jackson Heart Study

ObjectivesThis study examined the association of aldosterone and plasma renin activity (PRA) with incident cardiovascular disease (CVD), using a composite endpoint of coronary heart disease, stroke, and/or heart failure and mortality among African Americans in the Jackson Heart Study. BackgroundThere is a paucity of data for the association of aldosterone and PRA with incident CVD or all-cause mortality among community-dwelling African Americans. MethodsA total of 4,985 African American adults, 21 to 94 years of age, were followed for 12 years. Aldosterone, PRA, and cardiovascular risk factors were collected at baseline (from 2000 to 2004). Incident events included coronary heart disease and stroke (assessed from 2000 to 2011) and heart failure (assessed from 2005 to 2011). Cox models were used to estimate hazard ratios (HRs) for incident CVD and mortality, adjusting for age, sex, education, occupation, current smoking, physical activity, dietary intake, and body mass index. ResultsAmong 4,160 participants without prevalent CVD over a median follow-up of 7 years, there were 322 incident CVD cases. In adjusted analyses, each 1-U SD increase in log-aldosterone and log-PRA were associated with HR of 1.26 (95% confidence intervals [CI]: 1.14 to 1.40) and 1.16 (95% CI: 1.02 to 1.33) for incident CVD, respectively. Over a median of 8 years, 513 deaths occurred among 4,985 participants. In adjusted analyses, each 1-U SD increase in log-aldosterone and log-PRA were associated with HRs of 1.13 (95% CI: 1.04 to 1.23) and 1.12 (95% CI: 1.01 to 1.24) for mortality, respectively. ConclusionsElevated aldosterone and PRA may play a significant role in the development of CVD and all-cause mortality among African Americans.

Clinical course of tricuspid regurgitation in repaired tetralogy of Fallot

BackgroundLittle is known on the clinical course of tricuspid regurgitation (TR) in patients with repaired tetralogy of Fallot (rTOF) and which patients are at particular risk. This study aims to determine TR course, characteristics associated with TR progression, and the prognostic relevance of TR in rTOF patients. MethodsIn this dualcenter cohort study, rTOF patients from a prospective national registry with ≥1 cardiac magnetic resonance imaging study and ≥2 echocardiograms available were included. Clinical and imaging data were collected. Cox hazards regression analysis was used to assess patient characteristics associated with progression to severe TR and whether severe TR was associated with the combined clinical endpoint of tachyarrhythmia, heart failure, and death, as time-dependent factor. ResultsA total of 216 patients were included (57% men, age 34±12years); 11 patients (5%) had severe TR at baseline. During 7.6±3.5years of follow-up, progression to severe TR occurred in 15 patients (7%). NYHA class ≥2 (HR 5.38, 95%-C.I. 1.91–15.16, p=0.001) and moderate baseline TR (HR 13.10, 95%-C.I. 2.95–58.21, p=0.001) were independently associated with progression to severe TR. Adverse events occurred in 47 patients (22%). The occurrence of severe TR was independently associated with adverse events (HR 3.48, 95%-C.I. 1.68–7.21, p=0.001). ConclusionsIn this study, severe TR was present in 12% of adult rTOF patients during 7.6years, and progression to severe TR was most likely in symptomatic patients with moderate baseline TR. In these patients, close surveillance is warranted, because the occurrence of severe TR was associated with worse prognosis.

Association of Plasma 7-Ketocholesterol With Cardiovascular Outcomes and Total Mortality in Patients With Coronary Artery Disease.

7-Ketocholesterol (7-KC), a form of cholesterol oxidation product, plays an essential role in the atherogenesis in animal models. We sought to determine the association of circulating 7-KC with clinical cardiovascular outcomes and total mortality in patients with stable coronary artery disease. We measured the plasma 7-KC levels by high-performance liquid chromatography in a prospective cohort study of 1016 patients (mean age, 63.2 years; male 61.1%) with stable coronary artery disease who were recruited from December 2008 to December 2011 and followed up for a median of 4.6 years. We adjudicated myocardial infarction, hospitalization of heart failure, cardiovascular death, all-cause death, and composite end points of myocardial infarction/heart failure/death by review of medical records and death certificates. We used multivariable Cox proportional hazards analysis to compare the incidence rate of cardiovascular events and all-cause death according to the quartile of the plasma 7-KC. During the median 4.6 years follow-up, totally 221 participants (21.8%) experienced a cardiovascular event or death. The adjusted risk of the composite end points was higher in the highest 7-KC quartile than in the lowest quartile (hazard ratio, 1.76; 95% confidence interval, 1.42-2.21; P<0.001). After adjustment for demographic and clinical variables and other biomarkers, including high-sensitivity C-reactive protein and NT-proBNP (N-terminal pro-B-type natriuretic peptide), 1 SD increase in the 7-KC level remained associated with a 36% higher rate of composite outcomes (hazard ratio, 1.36; 95% confidence interval, 1.22-1.48; P=0.007). Plasma 7-KC clearly improved various model performance measures, including C statistics, integrated discrimination, and category-free net reclassification. High 7-KC levels are associated with increased risk of cardiovascular events, total death, and composite outcomes in patients with stable coronary artery disease.

Poor Response to Periodontal Treatment May Predict Future Cardiovascular Disease

Periodontal disease has been associated with cardiovascular disease (CVD), but whether the response to the treatment of periodontal disease affects this association has not been investigated in any large prospective study. Periodontal data obtained at baseline and 1 y after treatment were available in 5,297 individuals with remaining teeth who were treated at a specialized clinic for periodontal disease. Poor response to treatment was defined as having >10% sites with probing pocket depth >4 mm deep and bleeding on probing at ≥20% of the sites 1 y after active treatment. Fatal/nonfatal incidence rate of CVD (composite end point of myocardial infarction, stroke, and heart failure) was obtained from the Swedish cause-of-death and hospital discharge registers. Poisson regression analysis was performed to analyze future risk of CVD. During a median follow-up of 16.8 y (89,719 person-years at risk), those individuals who did not respond well to treatment (13.8% of the sample) had an increased incidence of CVD (n = 870) when compared with responders (23.6 vs. 15.3%, P < 0.001). When adjusting for calendar time, age, sex, educational level, smoking, and baseline values for bleeding on probing, probing pocket depth >4 mm, and number of teeth, the incidence rate ratio for CVD among poor responders was 1.28 (95% CI, 1.07 to 1.53; P = 0.007) as opposed to good responders. The incidence rate ratio among poor responders increased to 1.39 (95% CI, 1.13 to 1.73; P = 0.002) for those with the most remaining teeth. Individuals who did not respond well to periodontal treatment had an increased risk for future CVD, indicating that successful periodontal treatment might influence progression of subclinical CVD.

Effect of eplerenone in patients with heart failure and reduced ejection fraction: potential effect modification by abdominal obesity. Insight from the EMPHASIS-HF trial.

An excessive production of aldosterone influences outcome in patients with heart failure (HF) and in obese patients. Findings from laboratory studies suggest that chronic aldosterone blockade maybe more beneficial in abdominally obese HF-prone rats. In the current study, we investigated if the clinical response to a mineralocorticoid receptor antagonist in mildly symptomatic HF patients varied by abdominal obesity. A total of 2587 NYHA class II, reduced ejection fraction HF (HFrEF) patients enrolled in the EMPHASIS-HF trial were randomly assigned to eplerenone and placebo. In this post hoc analysis, patients were categorized according to waist circumference (WC) (normal if WC < 102 cm in men and < 88 cm in women; abdominal obesity if WC ≥ 102 cm in men and ≥ 88 cm women). The potential statistical interaction between the treatment and WC was assessed on the primary endpoint of death from cardiovascular causes or hospitalization for HF and other secondary endpoints. Over a median follow-up of 21 months, a significant benefit of eplerenone for the primary outcome was noted in both normal [hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.61-0.98, P = 0.03] and increased (HR 0.48, 95% CI 0.37-0.63, P < 0.0001) WC subgroups, but the latter patients appeared to receive greater benefit than patients with normal WC (P for interaction = 0.01). This suggests a significant quantitative (treatment effect varies in magnitude by subgroup, but is always in same direction) rather than a qualitative interaction (direction of the treatment effect varies by subgroup) between eplerenone and WC in the adjusted analysis. Mean doses of eplerenone, blood pressure and serum potassium changes and adverse events were similar between WC subgroups. In EMPHASIS-HF, eplerenone improved outcomes in HFrEF patients with and without abdominal obesity, although the benefit appeared to be more pronounced among those with abdominal obesity. The findings are potentially hypothesis generating and need to be replicated in other HFrEF populations.