Electrocardiogram to Determine Mitral and Aortic Valve Opening and Closure.

PURPOSE: Knowledge of the timing of cardiac valve opening and closing is important in cardiac physiology. The relationship between valve motion and electrocardiogram (ECG) is often assumed, however is not clearly defined. Here we investigate the accuracy of cardiac valve timing estimated using only the ECG, compared to Doppler echocardiography (DE) flow imaging as the gold standard. METHODS: DE was obtained in 37 patients with simultaneous ECG recording. ECG was digitally processed and identifiable features (QRS, T, P waves) were examined as potential reference points to determine opening and closure of aortic and mitral valves, as compared to DE outflow and inflow measurement. Timing offset of the cardiac valves opening and closure between ECG features and DE was measured from derivation set (n = 19). The obtained mean offset in combination with the ECG features model was then evaluated on a validation set (n = 18). Using the same approach, additional measurement was also done for the right sided valves. RESULTS: From the derivation set, we found a fixed offset of 22 ± 9 ms, 2 ± 13 ms, 90 ± 26 ms, and - 2 ± - 27 ms when comparing S to aortic valve opening, Tend to aortic valve closure, Tend to mitral valve opening, and R to mitral valve closure respectively. Application of this model to the validation set showed good estimation of aortic and mitral valve opening and closure timing value, with low model absolute error (median of the mean absolute error of the four events = 19 ms compared to the gold standard DE measurement). For the right-sided (tricuspid and pulmonic) valves in our patient set, there was considerably higher median of the mean absolute error of 42 ms for the model. CONCLUSION: ECG features can be used to estimate aortic and mitral valve timings with good accuracy as compared to DE, allowing useful hemodynamic information to be derived from this easily available test.

Echocardiographic diagnosis of left ventricular diastolic dysfunction: Impact of coronary artery disease.

BACKGROUND: In 2016, the American Society of Echocardiography (ASE) released guidelines for identifying left ventricular (LV) diastolic dysfunction (DD), but its ability to detect early hemodynamic abnormalities is not well established, especially in the setting of subclinical coronary artery disease (CAD). We hypothesize that the accuracy of ASE categorization of early LVDD is affected by knowledge of whether CAD history is present. METHODS: We studied 34 patients (age 62 ± 7 years) with NYHA class I to II symptoms and with transthoracic echocardiography without findings suggesting myocardial disease (all with preserved LV ejection fraction), who underwent cardiac catheterization with high-fidelity LV pressure measurement. Echocardiographic images were evaluated for LVDD using ASE algorithm without and with knowledge of CAD history and angiography findings. CAD was considered as having DD for the algorithm. RESULTS: CAD was identified in 22 patients at catheterization (65%). Using ASE guidelines without including history of CAD or angiographic results, 29 patients were DD-, 3 were DD+ (all grade II), and 2 were indeterminate. Inclusion of CAD history recategorized 59% (n = 20) patients to DD+ (all grade I) from DD- (P < .0001). Nineteen of the recategorized patients (95%) had increased isovolumetric relaxation time (IVRT). The addition of echocardiographic IVRT improved discrimination between DD- and DD+, when the presence of CAD is unknown. CONCLUSIONS: 2016-ASE algorithm reasonably accurately identifies early LVDD at rest as reflected by LV catheterization when CAD is disclosed, but without knowledge of the presence of CAD, it underdiagnoses DD+ grade I. The addition of IVRT may improve early LVDD diagnostics.

Risk of Major Adverse Cardiovascular Events and Major Hemorrhage Among White and Black Patients Undergoing Percutaneous Coronary Intervention.

Background Data on racial disparities in major adverse cardiovascular events (MACE) and major hemorrhage (HEM) after percutaneous coronary intervention are limited. Factors contributing to these disparities are unknown. Methods and Results PRiME-GGAT (Pharmacogenomic Resource to Improve Medication Effectiveness-Genotype-Guided Antiplatelet Therapy) is a prospective cohort. Patients aged ≥18 years undergoing percutaneous coronary intervention were enrolled and followed for up to 1 year. Racial disparities in risk of MACE and HEM were assessed using an incident rate ratio. Sequential cumulative adjustment analyses were performed to identify factors contributing to these disparities. Data from 919 patients were included in the analysis. Compared with white patients, black patients (n=203; 22.1% of the cohort) were younger and were more likely to be female, to be a smoker, and to have higher body mass index, lower socioeconomic status, higher prevalence of diabetes mellitus and moderate to severe chronic kidney disease, and presentation with acute coronary syndrome and to undergo urgent percutaneous coronary intervention. The incident rates of MACE (34.1% versus 18.2% per 100 person-years, P<0.001) and HEM (17.7% versus 10.3% per 100 person-years, P=0.02) were higher in black patients. The incident rate ratio was 1.9 (95% CI, 1.3-2.6; P<0.001) for MACE and 1.7 (95% CI, 1.1-2. 7; P=0.02) for HEM. After adjustment for nonclinical and clinical factors, black race was not significantly associated with outcomes. Rather, differences in socioeconomic status, comorbidities, and coronary heart disease severity were attributed to racial disparities in outcomes. Conclusions Despite receiving similar treatment, racial disparities in MACE and HEM still exist. Opportunities exist to narrow these disparities by mitigating the identified contributors.

Complete white out of a single transplanted lung in the immediate postoperative period.

Vascular complications are rare but serious events following lung transplantation. Of the potential adverse events post lung transplant, pulmonary vein thrombosis is rare but often fatal. Our case describes a 54 year-old male who underwent single left lung transplantation and suddenly became hemodynamically unstable shortly after the procedure. The diagnosis of acute pulmonary vein thrombosis was made with the use of trans-esophageal echocardiography identifying complete occlusion of the left upper pulmonary vein which led to successful surgical thrombectomy and revision of the anastomosis.

Left Ventricular Torsion Shear Angle Volume Approach for Noninvasive Evaluation of Diastolic Dysfunction in Preserved Ejection Fraction.

BACKGROUND: Accurate noninvasive diagnostic tools for evaluating left ventricular (LV) diastolic dysfunction (LVDD) are limited in preserved LV ejection fraction. We previously proposed the relationship of normalized rate of change in LV torsion shear angle (φ') to corresponding rate of change in LV volume (V') during early diastole (represented as -dφ'/dV') as a measure of LV diastolic function. We prospectively evaluated diagnostic accuracy of -dφ'/dV' in respect to invasive LV parameters. METHODS AND RESULTS: Participants (n=36, age 61±7 years) with LV ejection fraction ≥50% and no acute myocardial infarction undergoing coronary angiography for chest pain and/or dyspnea evaluation were studied. High-fidelity invasive LV pressure measurements and cardiac magnetic resonance imaging with tissue tagging were performed. τ, the time constant of LV diastolic relaxation, was 58±10 milliseconds (mean±SD), and LV end-diastolic pressure was 14.5±5.5 mm Hg. Cardiac magnetic resonance imaging-derived -dφ'/dV' was 5.6±3.7. The value of -dφ'/dV' correlated with both τ and LV end-diastolic pressure (r=0.39 and 0.36, respectively, P<0.05). LVDD was defined as τ>48 milliseconds and LV end-diastolic pressure >12 mm Hg (LVDD1), or, alternatively, τ>48 milliseconds and LV end-diastolic pressure >16 mm Hg (LVDD2). Area under the curve (AUC) of -dφ'/dV' for identifying LVDD1 was 0.83 (0.67-0.98, P=0.001), with sensitivity/specificity of 72%/100% for -dφ'/dV' ≥6.2. AUC of -dφ'/dV' for identifying LVDD_2 was 0.82 (0.64-1.00, P=0.006), with sensitivity/specificity of 76%/85% for -dφ'/dV' ≥6.9. There were good limits of agreement between pre- and post-nitroglycerin -dφ'/dV'. CONCLUSIONS: The -dφ'/dV' obtained from the LV torsion volume loop is a promising parameter for assessing global LVDD with preserved LV ejection fraction and requires further evaluation.

Left ventricular diastolic function and exercise capacity in community-dwelling adults ≥65 years of age without heart failure.

Left ventricular diastolic dysfunction (LVDD) has been reported to have strong correlation with exercise capacity. However, this relationship has not been studied extensively in community-dwelling older adults. Data on pulse and tissue Doppler echocardiographic estimates of resting early (E) and atrial (A) transmitral peak inflow and early (Em) mitral annular velocities, and six-minute walk test were obtained from 89 community-dwelling older adults (mean age, 74; range, 65-93 years; 54% women), without a history of heart failure. Overall, 47% had cardiovascular morbidity and 60% had normal diastolic function (E/A 0.75-1.5 and E:Em <10). Among the 36 individuals with LVDD, 83%, 14% and 3% had grade I (E/A <0.75, regardless of E/E(m)), II (E/A 0.75-1.5 and E/E(m) ≥10) and III (E/A>1.5 and E/E(m) ≥10) LVDD, respectively. Those with LVDD were older (77 versus 73 years; p = 0.001) and had a trend for higher prevalence of cardiovascular morbidity (58% versus 40%; p = 0.083). LVDD negatively correlated with six-minute walk distance (1013 versus 1128 feet; R = -0.25; p = 0.017). This association remained significant despite adjustment for cardiovascular morbidity (R = -0.35; p = 0.048), but lost significance when adjusted for age (R = -0.32; p = 0.105), age and cardiovascular morbidity (R = -0.38; p = 0.161), and additional adjustment for sex, race, body mass index, and systolic blood pressure (R = -0.44; p = 0.365). In conclusion, most community-dwelling older adults without heart failure had normal left ventricular diastolic function or grade-I LVDD. Although LVDD was associated with decreased performance on a six-minute walk test, that association was no longer evident after adjustment for age, body mass index and cardiovascular morbidity.

Effects of right ventricular ejection fraction on outcomes in chronic systolic heart failure.

BACKGROUND: Studies of the effect of right ventricular ejection fraction (RVEF) on outcomes in heart failure (HF) are limited by small sample size and short follow-up. METHODS AND RESULTS: We examined the effect of baseline RVEF on outcomes in 2008 Beta-Blocker Evaluation of Survival Trial (BEST) participants with HF and left ventricular ejection fraction or=40% (n=733), 30% to 39% (n=531), 20% to 29% (n=473), and <20% (n=271). Unadjusted rates for all-cause mortality in patients with RVEF >or=40%, 30% to 39%, 20% to 29%, and <20% were 27%, 32%, 35%, and 47%, respectively. When compared with patients with RVEF >or=40%, unadjusted hazard ratios and 95% confidence intervals for all-cause mortality for those with RVEF 30% to 39%, 20% to 29%, and <20% were 1.19 (0.97 to 1.46; P=0.087), 1.45 (1.17 to 1.78; P=0.001), and 1.98 (1.59 to 2.47; P<0.0001), respectively. Respective multivariable-adjusted hazard ratios (95% confidence intervals) for all-cause mortality associated with RVEF 30% to 39%, 20% to 29%, and <20% were 1.07 (0.87 to 1.32; P=0.518), 1.12 (0.89 to 1.40; P=0.328), and 1.32 (1.02 to 1.71; P=0.034), respectively. Adjusted hazard ratios (95% confidence intervals) for other outcomes associated with RVEF <20% (compared with >or=40%) were as follows: cardiovascular mortality, 1.33 (1.01 to 1.76; P=0.041); HF mortality, 1.61 (1.03 to 2.52; P=0.037); sudden cardiac death, 1.29 (0.87 to 1.91; P=0.212); all-cause hospitalization, 1.21 (1.00 to 1.47; P=0.056); and HF hospitalization, 1.39 (1.10 to 1.77; P=0.007). CONCLUSIONS: Baseline RVEF <20% is a significant independent predictor of mortality and HF hospitalization in systolic HF.

Mild hyperkalemia and outcomes in chronic heart failure: a propensity matched study.

BACKGROUND: Compared with serum potassium levels 4-5.5 mEq/L, those <4 mEq/L have been shown to increase mortality in chronic heart failure (HF). Expert opinions suggest that serum potassium levels >5.5 mEq/L may be harmful in HF. However, little is known about the safety of serum potassium 5-5.5 mEq/L. METHODS: Of the 7788 chronic HF patients in the Digitalis Investigation Group trial, 5656 had serum potassium 4-5.5 mEq/L. Of these, 567 had mild hyperkalemia (5-5.5 mEq/L) and 5089 had normokalemia (4-4.9 mEq/L). Propensity scores for mild hyperkalemia were used to assemble a balanced cohort of 548 patients with mild hyperkalemia and 1629 patients with normokalemia. Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for association between mild hyperkalemia and mortality during a median follow-up of 38 months. RESULTS: All-cause mortality occurred in 36% and 38% of matched patients with normokalemia and mild hyperkalemia respectively (HR, 1.07; 95% CI, 0.90-1.26; P=0.458). Unadjusted, multivariable-adjusted, and propensity-adjusted HRs for mortality associated with mild hyperkalemia were 1.33 (95% CI, 1.15-1.52; P<0.0001), 1.16 (95% CI, 1.01-1.34; P=0.040) and 1.13 (95% CI, 0.98-1.31; P=0.091) respectively. Mild hyperkalemia had no association with cardiovascular or HF mortality or all-cause or cardiovascular hospitalization. CONCLUSION: Serum potassium 4-4.9 mEq/L is optimal and 5-5.5 mEq/L appears relatively safe in HF. Despite lack of an intrinsic association , the bivariate association of mild-hyperkalemia with mortality suggests that it may be useful as a biomarker of poor prognosis in HF.

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.

A dual propagation contours technique for semi-automated assessment of systolic and diastolic cardiac function by CMR.

BACKGROUND: Although cardiovascular magnetic resonance (CMR) is frequently performed to measure accurate LV volumes and ejection fractions, LV volume-time curves (VTC) derived ejection and filling rates are not routinely calculated due to lack of robust LV segmentation techniques. VTC derived peak filling rates can be used to accurately assess LV diastolic function, an important clinical parameter. We developed a novel geometry-independent dual-contour propagation technique, making use of LV endocardial contours manually drawn at end systole and end diastole, to compute VTC and measured LV ejection and filling rates in hypertensive patients and normal volunteers. METHODS: 39 normal volunteers and 49 hypertensive patients underwent CMR. LV contours were manually drawn on all time frames in 18 normal volunteers. The dual-contour propagation algorithm was used to propagate contours throughout the cardiac cycle. The results were compared to those obtained with single-contour propagation (using either end-diastolic or end-systolic contours) and commercially available software. We then used the dual-contour propagation technique to measure peak ejection rate (PER) and peak early diastolic and late diastolic filling rates (ePFR and aPFR) in all normal volunteers and hypertensive patients. RESULTS: Compared to single-contour propagation methods and the commercial method, VTC by dual-contour propagation showed significantly better agreement with manually-derived VTC. Ejection and filling rates by dual-contour propagation agreed with manual (dual-contour - manual PER: -0.12 +/- 0.08; ePFR: -0.07 +/- 0.07; aPFR: 0.06 +/- 0.03 EDV/s, all P = NS). However, the time for the manual method was approximately 4 hours per study versus approximately 7 minutes for dual-contour propagation. LV systolic function measured by LVEF and PER did not differ between normal volunteers and hypertensive patients. However, ePFR was lower in hypertensive patients vs. normal volunteers, while aPFR was higher, indicative of altered diastolic filling rates in hypertensive patients. CONCLUSION: Dual-propagated contours can accurately measure both systolic and diastolic volumetric indices that can be applied in a routine clinical CMR environment. With dual-contour propagation, the user interaction that is routinely performed to measure LVEF is leveraged to obtain additional clinically relevant parameters.

The scope of coronary heart disease in patients with chronic kidney disease.

Chronic kidney disease (CKD) affects approximately 13% of the U.S. population and is associated with increased risk of cardiovascular complications. Once renal replacement therapy became available, it became apparent that the mode of death of patients with advanced CKD was more likely than not related to cardiovascular compromise. Further observation revealed that such compromise was related to myocardial disease (related to hypertension, stiff vessels, coronary heart disease, or uremic toxins). Early on, the excess of cardiovascular events was attributed to accelerated atherosclerosis, inadequate control of blood pressure, lipids, or inflammatory cytokines, or perhaps poor glycemia control. In more recent times, outcome research has given us further information that relates even lesser degrees of renal compromise to an excess of cardiovascular events in the general population and in those with already present atherosclerotic disease. As renal function deteriorates, certain physiologic changes occur (perhaps due to hemodynamic, inflammatory, or metabolic changes) that decrease oxygen-carrying capacity of the blood by virtue of anemia, make blood vessels stiffer by altering collagen or through medial calcinosis, raise the blood pressure, increase shearing stresses, or alter the constituents of atherosclerotic plaque or the balance of thrombogenesis and thrombolysis. At further levels of renal dysfunction, tangible metabolic perturbations are recognized as requiring specific therapy to reduce complications (such as for anemia and hyperparathyroidism), although outcome research to support some of our current guidelines is sorely lacking. Understanding the process by which renal dysfunction alters the prognosis of cardiac disease might lead to further methods of treatment. This review will outline the relationship of CKD to coronary heart disease with respect to the current understanding of the traditional and nontraditional risk factors, the role of various imaging modalities, and the impact of coronary revascularization on outcome.

Systolic dysfunction portends increased mortality among those waiting for renal transplant.

Individuals waiting for a renal transplant experience excessive cardiovascular mortality, which is not fully explained by the prevalence of ischemic heart disease in this population. Overt heart failure is known to increase the mortality of patients with ESRD, but the impact of lesser degrees of ventricular systolic dysfunction is unknown. For examination of the association between left ventricular ejection fraction(LVEF) and mortality of renal transplant candidates, the records of 2718 patients evaluated for transplantation at one institution were reviewed. During 6355 patient-years (median 27 mo) of follow-up, 681 deaths occurred. Patients with systolic dysfunction (LVEF

Predictors of survival in patients with end-stage renal disease evaluated for kidney transplantation.

Cardiovascular disease is the major cause of mortality in patients with end-stage renal disease (ESRD). This study examined the all-cause mortality in 3,698 patients with ESRD evaluated for kidney transplantation at our institution from 2001 to 2004. Mean age for the cohort was 48+/-12 years, and 42% were women. Stress myocardial perfusion imaging was done in 2,207 patients (60%) and coronary angiography in 260 patients (7%). There were 622 deaths (17%) during a mean follow-up period of 30+/-15 months. The presence and severity of coronary disease on angiography was not predictive of survival. Coronary revascularization did not impact survival (p=0.6) except in patients with 3-vessel disease (p=0.05). The best predictor of death was left ventricular ejection fraction, measured by gated myocardial perfusion imaging, with 2.7% mortality increase for each 1% ejection fraction decrease. In conclusion, left ventricular ejection fraction is a strong predictor of survival in patients with ESRD awaiting renal transplantation. Strategies to improve cardiac function or earlier renal transplantation deserve further studies.

Origin of all three major coronary arteries from the right sinus of Valsalva: clinical, angiographic, and magnetic resonance imaging findings and incidence in a select referral population.

OBJECTIVE: We sought to determine the incidence and imaging features by coronary angiography and cardiac magnetic resonance imaging (MRI) of anomalies in which the right, circumflex, and left anterior descending coronary arteries arise separately from the right sinus of Valsalva. BACKGROUND: The anomalous origin of all major coronary arteries from separate ostia in the right sinus of Valsalva has been reported as exceedingly rare, with mainly isolated cases reported. A knowledge of the origin and proximal courses of aberrant arteries is critical for patient management. METHODS: 42 consecutive patients without other congenital heart disease referred to our institution for MRI evaluation of anomalous coronary artery over a six year period were evaluated. Analysis of angiograms and MRI was done to determine the anatomic origin and proximal pathway of coronary arteries (determined by conventional angiography and MRI) and degree of any stenosis (by angiography). RESULTS: Seven of the 42 patients (17%) in this referral population had the described anatomy. Both conventional angiography and MRI depicted the origin and proximal courses of these arteries. In all patients, the circumflex passed behind the aorta. In three, the left anterior descending passed through the ventricular septum; in four, it passed anterior to the pulmonary trunk. CONCLUSIONS: This series is the largest ever reported on this complex anatomical variant and the first to give a systematic analysis of the anatomy by angiography and MRI. This constellation of multiple anomalous coronary arterial origins and proximal courses may not be as rare as previously reported.

Chronic kidney disease associated mortality in diastolic versus systolic heart failure: a propensity matched study.

Chronic kidney disease (CKD) is common and is associated with increased mortality in heart failure (HF). However, it is unknown whether the effect of CKD on mortality varies by left ventricular ejection fraction (LVEF). We evaluated the effect of CKD on mortality in patients with systolic (LVEF 45%) HF. Of the 7,788 patients in the Digitalis Investigation Group trial, 3,527 (45%) had CKD (estimated glomerular filtration rate <60 ml/min/1.73 m2). We calculated the propensity score for CKD for each patient, using a multivariate logistic regression model (c statistic 0.76, postmatch absolute standardized differences <5% for all 32 co-variates). We matched 2,399 pairs of patients with and without CKD with similar propensity scores. There were 757 (rate 1,049/10,000 person-years) and 882 (rate 1,282/10,000 person-years) deaths, respectively, in patients without and with CKD (hazard ratio 1.22, 95% confidence interval 1.09 to 1.36, p <0.0001). CKD-associated mortality was higher in those with diastolic HF (371 extra deaths/10,000 person-years, hazard ratio 1.71, 95% confidence interval 1.21 to 2.41, p = 0.002) than in systolic HF (214 extra deaths/10,000 person-years, hazard ratio 1.19, 95% confidence interval 1.07 to 1.32, p = 0.001), which was significant (adjusted p for interaction = 0.034). A graded association was found between CKD-related deaths and LVEF. The hazard ratios for CKD-associated mortality for the LVEF subgroups of <35%, 35% to 55%, and >55% were 1.15 (95% confidence interval 1.02 to 1.29), 1.35 (95% confidence interval 1.11 to 1.64), and 2.33 (95% confidence interval 1.34 to 4.06). In conclusion, CKD-associated mortality was higher in those with diastolic than systolic HF. Patients with diastolic HF should be evaluated for CKD, and the role of inhibitors of the renin-angiotensin system in these patients needs to be investigated.

Outcomes in ambulatory chronic systolic and diastolic heart failure: a propensity score analysis.

BACKGROUND: Prior studies demonstrating significant difference in outcomes in systolic and diastolic heart failure (HF) are often limited to hospitalized acute HF patients, and may be confounded by residual bias. In this analysis, we examined long-term mortality and hospitalization in a propensity score matched cohort of ambulatory chronic systolic and diastolic HF patients. METHODS: Of the 7788 patients in the Digitalis Investigation Group trial, 6800 had systolic HF (ejection fraction >45%) and 988 had diastolic HF (ejection fraction >45%). We restricted our analysis to 7617 patients without valvular heart disease: 916 diastolic HF and 6701 systolic HF. Propensity scores for diastolic HF, calculated for each patient by a non-parsimonious multivariable logistic regression model, were used to match 697 diastolic HF with 2091 systolic HF patients. Matched Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for outcomes in diastolic (versus systolic) HF. RESULTS: During a median 38-month follow-up, compared with 32% mortality in systolic HF, 23% of diastolic HF patients died (HR=0.70; 95% CI=0.59-0.84; P<.0001). Respective HR (95%CI) for cardiovascular and HF mortality were 0.60 (0.48-0.74; P<.0001) and 0.56 (0.39-0.79; P=.001). All-cause hospitalizations occurred in 64% of systolic and 67% of diastolic HF patients (HR=0.99; 95% CI=0.87-1.11; P=0.801). Respective HR (95%CI) for cardiovascular and HF hospitalizations were 0.84 (0.73-0.96; P=.011) and 0.63 (0.51-0.77; P<.0001). CONCLUSIONS: Despite lower mortality and cardiovascular morbidity, diastolic HF patients had similar overall hospitalizations as in systolic HF. Ejection fraction should be assessed in all HF patients to guide therapy, with special attention to non-cardiovascular morbidity in diastolic HF.

Eplerenone prevents adverse cardiac remodelling induced by pressure overload in atrial natriuretic peptide-null mice.

1. Atrial natriuretic peptide (ANP)-null mice (Nppa(-/-)) exhibit cardiac hypertrophy at baseline and adverse cardiac remodelling in response to transverse aortic constriction (TAC)-induced pressure overload stress. Previous studies have suggested that natriuretic peptides could potentially oppose mineralocorticoid signalling at several levels, including suppression of adrenal aldosterone production, inhibition of mineralocorticoid receptor (MR) activation or suppression of MR-mediated production of pro-inflammatory factors. Thus, we hypothesized that the MR blocker eplerenone would prevent the exaggerated left ventricular (LV) remodelling/fibrosis and dysfunction after TAC in Nppa(-/-). 2. In the present study, Nppa(-/-) and wild-type Nppa(+/+) mice fed eplerenone- or vehicle (oatmeal)-supplemented chow since weaning were subjected to TAC or sham operation. The daily dose of eplerenone administered was approximately 200 mg/kg. At 1 week after TAC, LV size and function were evaluated by echocardiogram and LV cross-sections were stained with picrosirius red for collagen volume measurement. Total RNA was extracted from the LV for real-time polymerase chain reaction analysis of osteopontin. 3. Eplerenone had no effect on baseline hypertrophy observed in sham-operated Nppa(-/-) compared with Nppa(+/+) mice. Eplerenone attenuated the TAC-induced increase in LV weight in both genotypes and completely prevented LV dilation, systolic dysfunction and interstitial collagen deposition seen in Nppa(-/-) mice after TAC. However, serum aldosterone levels were lower in Nppa(-/-) compared with Nppa(+/+) wild types. No interaction between eplerenone and genotype in osteopontin mRNA levels was observed. 4. Eplerenone prevents adverse cardiac remodelling related to pressure overload in ANP-deficient mice, mainly due to an antifibrotic effect. The mechanism whereby ANP deficiency leads to excess hypertrophy, fibrosis and early failure following TAC is increased profibrotic signals resulting from excess or unopposed MR activation, rather than increased levels of aldosterone.

Incident atrial fibrillation and mortality in older adults with heart failure.

We studied 944 hospitalized heart failure patients 65 years and older to examine the impact of incident atrial fibrillation on mortality. Patients were categorized into four groups based on past medical history and admission electrocardiogram: (1) no (neither past nor current), (2) incident (newly diagnosed), (3) past and (4) chronic (past and current) atrial fibrillation. The primary outcome was 4-year all-cause mortality. Bivariate and multivariable Cox proportion hazards analyses were used to determine risk of all-cause mortality. In the multivariable model, we adjusted for various demographic and clinical covariates. Compared with patients who never had atrial fibrillation, those with incident atrial fibrillation had a 57% higher risk of death (unadjusted hazard ratio, 1.57; 95% confidence interval, 1.22-2.03). After adjustment for other covariates the association remained unchanged (adjusted hazard ratio, 1.41; 95% confidence interval, 1.08-1.83). Past or chronic atrial fibrillation was not associated with increased risk of death.

A propensity score analysis of the impact of angiotensin-converting enzyme inhibitors on long-term survival of older adults with heart failure and perceived contraindications.

OBJECTIVES: The purpose of this study is to determine the association between discharge use of angiotensin-converting enzyme (ACE) inhibitors in patients with perceived contraindications to these drugs and 4-year post-discharge survival among hospitalized older adults discharged alive with a primary discharge diagnosis of systolic heart failure. BACKGROUND: Perceived contraindications to the use of ACE inhibitors are often associated with underuse of these life-saving drugs. METHODS: Chronic renal insufficiency, hypotension, hyperkalemia, and severe aortic stenosis were conditions perceived as contraindications. Using a multivariable logistic regression model, we at first determined propensity scores for receipt of ACE inhibitors for each patient. Bivariate and multivariable Cox proportional hazard analyses were used to determine crude and adjusted risks of 4-year mortality compared with patients without perceived contraindications who were discharged on an ACE inhibitor (referent group). RESULTS: Compared with the referent group, patients with perceived contraindications who were not discharged on an ACE inhibitor had a significant 2-fold increase in the risk of 4-year mortality (adjusted hazard ratio [HR] = 2.33, 95% CI = 1.30-4.19). Patients with perceived contraindications who were discharged on ACE inhibitors had a non significant 23% higher risk of 4-year mortality (versus the referent group) (adjusted HR = 1.23, 95% CI = 0.71-2.13). CONCLUSION: Discharge use of ACE inhibitors was associated with significant long-term survival benefit in patients considered to have contraindication to these drugs.