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Background: In patients with heart failure, chronic kidney disease is common and associated with a higher risk of renal events than in patients without chronic kidney disease. We assessed the renal effects of angiotensin/neprilysin inhibition in patients who have heart failure with preserved ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction)., Methods: In this randomized, double-blind, event-driven trial, we assigned 4822 patients who had heart failure with preserved ejection fraction to receive sacubitril/valsartan (n=2419) or valsartan (n=2403). Herein, we present the results of the prespecified renal composite outcome (time to first occurrence of either: ≥50% reduction in estimated glomerular filtration rate (eGFR), end-stage renal disease, or death from renal causes), the individual components of this composite, and the influence of therapy on eGFR slope., Results: At randomization, eGFR was 63±19 mL·min -1 ·1.73 m - 2. At study closure, the composite renal outcome occurred in 33 patients (1.4%) assigned to sacubitril/valsartan and 64 patients (2.7%) assigned to valsartan (hazard ratio, 0.50 [95% CI, 0.33-0.77]; P =0.001). The treatment effect on the composite renal end point did not differ according to the baseline eGFR (<60 versus ≥60 mL·min -1 ·1.73 m -2 ( P -interaction=0.92). The decline in eGFR was less for sacubitril/valsartan than for valsartan (-2.0 [95% CI, -2.2 to -1.9] versus -2.7 [95% CI, -2.8 to -2.5] mL·min -1 ·1.73 m -2 per year)., Conclusions: In patients with heart failure with preserved ejection fraction, sacubitril/valsartan reduced the risk of renal events, and slowed decline in eGFR, in comparison with valsartan. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.

The symptom cluster of shortness of breath (SOB) contributes significantly to the outpatient workload of cardiology services. The workup of these patients includes blood chemistry and biomarkers, imaging and functional testing of the heart and lungs. A diagnosis of diastolic heart failure is inferred through the exclusion of systolic abnormalities, a normal pulmonary function test and normal hemoglobin, coupled with diastolic abnormalities on echocardiography. Differentiating confounders such as obesity or deconditioning in a patient with diastolic abnormalities is difficult. While the most recent guidelines provide more avenues for diagnosis, such as incorporating the left atrial size, little emphasis is given to understanding left atrial function, which contributes to at least 25% of diastolic left ventricular filling; additionally, exercise stress testing to elicit symptoms and test the dynamics of diastolic parameters, especially when access to the "gold standard" invasive tests is lacking, presents clinical translational gaps. It is thus important in diastolic heart failure work up to understand left atrial mechanics and the role of exercise testing to build a comprehensive argument for the diagnosis of diastolic heart failure in a patient presenting with SOB., Competing Interests: Conflict-of-interest statement: All co-authors have secured independent and governmental research funding. None pose a conflict of interest for this review.

A 69-year-old man with a history of ischaemic heart disease and previous stent implantation in the right coronary artery (RCA) was found to have a large well-encapsulated mass attached to the right atrium on a routine transthoracic echocardiogram. Subsequent investigations including transoesophageal echocardiography and CT coronary angiogram suggested an RCA aneurysm formation in relation to the prior stented segment, further confirming on coronary angiogram a large ectatic vessel with a giant aneurysm measuring 2.4×2.7 cm. Giant coronary artery aneurysms are rare and here we present interesting images of a case initially picked up on transthoracic echocardiography.

Heart failure mortality is significantly increased in patients with baseline renal impairment and those with underlying heart failure who subsequently develop renal dysfunction. This accelerated progression occurs independent of the cause or grade of renal dysfunction and baseline risk factors. Recent large prospective databases have highlighted the depth of the current problem, while longitudinal population studies support an increasing disease burden. We have extensively reviewed the epidemiological and therapeutic data among these patients. The evidence points to a progression of heart failure early in renal impairment, even in the albuminuric stage. The data also support poor prescription of prognostic therapies. As renal function is the most important prognostic factor in heart failure, it is important to establish the current understanding of the disease burden and the therapeutic implications.

The term 'cardiorenal syndrome' (CRS) has increasingly been used in recent years without a constant meaning and a well-accepted definition. To include the vast array of interrelated derangements, and to stress the bidirectional nature of the heart-kidney interactions, the classification of the CRS today includes 5 subtypes whose etymology reflects the primary and secondary pathology, the time frame and simultaneous cardiac and renal codysfunction secondary to systemic disease. The CRS can generally be defined as a pathophysiological disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ. Type I CRS reflects an abrupt worsening of cardiac function (e.g. acute cardiogenic shock or decompensated congestive heart failure) leading to acute kidney injury. Type II CRS describes chronic abnormalities in cardiac function (e.g. chronic congestive heart failure) causing progressive and permanent chronic kidney disease. Type III CRS consists in an abrupt worsening of renal function (e.g. acute kidney ischemia or glomerulonephritis) causing acute cardiac disorder (e.g. heart failure, arrhythmia, ischemia). Type IV CRS describes a state of chronic kidney disease (e.g. chronic glomerular disease) contributing to decreased cardiac function, cardiac hypertrophy and/or increased risk of adverse cardiovascular events. Type V CRS reflects a systemic condition (e.g. diabetes mellitus, sepsis) causing both cardiac and renal dysfunction. Biomarkers can help to characterize the subtypes of the CRS and to indicate treatment initiation and effectiveness. The identification of patients and the pathophysiological mechanisms underlying each syndrome subtype will help to understand clinical derangements, to make the rationale for management strategies and to design future clinical trials with accurate selection and stratification of the studied population.

Renal dysfunction is an independent risk factor for cardiovascular (cv) disease and its associated complications. Diabetes mellitus (dm) is a common cause of renal dysfunction. Whether the presence or absence of dm modifies the relation between renal dysfunction and cv disease is unclear. The valiant trial identified 14,527 patients with acute myocardial infarction complicated by either clinical or radiologic signs of heart failure and/or left ventricular dysfunction for whom baseline creatinine was measured. Patients were randomly assigned to receive captopril, valsartan, or both. Glomerular filtration rate (gfr) was estimated using the 4-component modification of diet in renal disease equation. Using multivariable cox proportional modeling, the relation of overall mortality and composite cardiovascular events with estimated gfr (egfr) between patients with and without dm was compared. Mean egfrs were 66.8 +/- 22.0 and 71.2 +/- 21.0 ml/min/1.73 m2 for patients with (n = 3,358) and without dm (n = 11,169), respectively. The likelihood of experiencing death or the composite end point was higher in patients with than without dm for each level of renal function. the augmentation in risk of cv events based on reduced renal function was similar between groups. Each decrease in egfr by 10 units was associated with hazards of 1.09 (95% confidence interval 1.06 to 1.12, p <0.001) in patients with dm and 1.08 (95% confidence interval 1.06 to 1.10, p <0.001) in patients without dm for risk of fatal and nonfatal cv outcomes independent of treatment assignment. In conclusion, although dm is associated with higher risk of renal dysfunction and adverse cv outcomes, patients without dm had a relation between renal function and cv risk similar to that for patients with dm after high-risk acute myocardial infarction.

Severe right ventricular dysfunction independent of left ventricular ejection fraction increased the risk of heart failure (HF) and death after myocardial infarction (MI). The association between right ventricular function and other clinical outcomes after MI was less clear. Two-dimensional echocardiograms were obtained in 605 patients with left ventricular dysfunction and/or clinical/radiologic evidence of HF from the VALIANT echocardiographic substudy (mean 5.0 +/- 2.5 days after MI). Clinical outcomes included all-cause mortality, cardiovascular (CV) death, sudden death, HF, and stroke. Baseline right ventricular function was measured in 522 patients using right ventricular fractional area change (RVFAC) and was related to clinical outcomes. Mean RVFAC was 41.9 +/- 4.3% (range 19.2% to 53.1%). The incidence of clinical events increased with decreasing RVFAC. After adjusting for 11 covariates, including age, ejection fraction, and Killip's classification, decreased RVFAC was independently associated with increased risk of all-cause mortality (hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.31 to 1.98), CV death (HR 1.62, 95% CI 1.30 to 2.01), sudden death (HR 1.79, 95% CI 1.26 to 2.54), HF (HR 1.48, 95% CI 1.17 to 1.86), and stroke (HR 2.95, 95% CI 1.76 to 4.95), but not recurrent MI. Each 5% decrease in baseline RVFAC was associated with a 1.53 (95% CI 1.24 to 1.88) increased risk of fatal and nonfatal CV outcomes. In conclusion, decreased right ventricular systolic function is a major risk factor for death, sudden death, HF, and stroke after MI.

Objectives: The purpose of this study was to determine whether alterations in cardiac structure or function contribute to the increased risk associated with renal impairment after myocardial infarction (MI)., Background: Renal impairment is associated with adverse cardiovascular outcomes after MI., Methods: Echocardiography was performed on 603 patients with left ventricular (LV) dysfunction, heart failure (HF), or both after MI. Patients were grouped according to their estimated glomerular filtration rate (eGFR), and measures of cardiac structure and function were related to baseline eGFR. The relationship between eGFR and cardiac structure and function and clinical outcomes of death or HF was assessed with multivariable Cox regression., Results: Ejection fraction, infarct segment length, right ventricular function, and mitral deceleration time were not influenced by renal function. Patients with reduced eGFR had smaller LV and larger left atrial (LA) volumes and higher left ventricular mass index (LVMI) and LV mass/LV volume ratio. A greater proportion of the patients with reduced eGFR had LV hypertrophy. The relationship between eGFR and the outcome of death or HF was attenuated by including baseline differences in LVMI, and both LVMI and LA volume conferred additional prognostic information in a multivariable model., Conclusions: Renal impairment was associated with smaller LV and larger LA volumes and increased LVMI. Systolic function was similar when compared with patients with normal renal function. Thus, reduced systolic function cannot account for worse outcomes in patients with renal impairment after MI. Indirect measures of diastolic function suggest that diastolic dysfunction might be an important mediator of increased risk in this population.

Background: Embolism is a dreaded complication of infective endocarditis (IE). Currently, antimicrobial therapy is the only medical intervention proven to decrease the risk of embolism associated with IE. We hypothesized that, because platelet aggregation is operative in the pathogenesis of vegetation formation, embolism associated with IE should occur less frequently among patients who have received prior, continuous daily antiplatelet therapy for noninfectious reasons., Methods: We studied a retrospective cohort of adult patients with a diagnosis of IE who presented to the Mayo Clinic (Rochester, MN) during 1980-1998. The cohort was divided into 2 groups on the basis of whether they had received continuous daily antiplatelet therapy for at least 6 months prior to the time of hospitalization for IE. Antiplatelet therapy included aspirin, dipyridamole, clopidogrel, ticlopidine, or any of combination of these agents. The primary end point was a symptomatic embolic event that occurred prior to or during hospitalization. Multivariable logistic regression was used to assess the impact of continuous daily antiplatelet therapy on risk of symptomatic emboli associated with IE., Results: One hundred forty-seven (24.5%) of 600 patients experienced a symptomatic embolic event; the most common embolic manifestation was stroke (in 48.2% of patients). Embolic events occurred significantly less often among those who had received prior, continuous daily antiplatelet therapy (12.0% of patients who had received therapy vs. 27.8% patients who had not receive therapy; P<.001). After adjustment for several covariates known to influence both risk of embolism and propensity for antiplatelet use, the adjusted odds ratio for a symptomatic embolic event was 0.36 (95% confidence interval, 0.19-0.68; P=.002) for patients receiving continuous daily antiplatelet therapy., Conclusions: The risk of symptomatic emboli associated with IE was reduced in patients who received continuous daily antiplatelet therapy before onset of IE.

Background: While echocardiography is used most frequently to assess right ventricular (RV) function in clinical practice, echocardiography is limited in its ability to provide an accurate measure of RV ejection fraction (RVEF). Hence, quantitative estimation of RV function has proven difficult in clinical practice., Objective: We sought to determine which commonly used echocardiographic measures of RV function were most accurate in comparison with an MRI-derived estimate of RVEF., Methods: We analyzed RV function in 36 patients who had cardiac MRI studies and echocardiograms within a 24 hour period. 2D parameters of RV function-right ventricular fractional area change (RVFAC), tricuspid annular motion (TAM), and transverse fractional shortening (TFS) were obtained from the four-chamber view. RV volumes and EFs were derived from volumetric reconstruction based on endocardial tracing of the RV chamber from the short axis images. Echocardiographic assessment of RV function was correlated with MRI findings., Results: RVFAC measured by echocardiography correlated best with MRI-derived RVEF (r = 0.80, P < 0.001). Neither TAM (r = 0.17; P = 0.30) nor TFC (r = 0.12; p< 0.38) were significantly correlated with RVEF., Conclusions: RVFAC is the best of commonly utilized echocardiographic 2D measure of RV function and correlated best with MRI-derived RV ejection fraction., Condensed Abstract: While echocardiography is used most frequently to assess RV function in clinical practice, echocardiography is limited in its ability to provide an accurate measure of RV ejection fraction (RVEF). Using cardiac MRI, RV fractional area change (RVFAC), determined either by MRI or echocardiography, was found to correlate best with MRI-derived RVEF.

Background: Left ventricular (LV) ejection fraction (EF) and wall-motion index (WMI) have both been shown to be independent predictors of outcome after myocardial infarction (MI)., Objectives: We sought to determine whether these two measurements of LV systolic function provide similar or complementary information about prognosis after MI., Methods: Echocardiography was performed in 610 patients with LV dysfunction, heart failure, or both after MI enrolled in the Valsartan in Acute MI trial. LVEF was estimated by biplane Simpson's rule, and WMI was assessed using a 16-segment model in 502 patients with echocardiograms of sufficient quality for wall-motion assessment., Results: Both LVEF and WMI were independent predictors of adverse outcome after MI. LVEF conferred no additional prognostic information in multivariable analysis including WMI (P = .39) or number of affected segments (P = .53), whereas WMI (P = .02) and total number of affected segments (P = .006) remained significant even when adjusting for LVEF., Conclusions: Assessment of regional dysfunction by WMI or the number of affected segments has slightly more prognostic value than LVEF in patients with LV dysfunction, heart failure, or both after MI. Regional assessment might be a more sensitive predictor of outcome than global assessment in patients with acute MI.

Purpose: While both first-pass perfusion and late gadolinium enhancement by cardiovascular magnetic resonance (CMR) can assess coronary microvascular status in acute myocardial infarction (AMI), there are only limited data on their respective diagnostic utility. We aim to evaluate: the utility of first-pass perfusion and late gadolinium enhancement imaging in the detection and quantification of microvascular dysfunction after reperfused acute myocardial infarction, using TIMI frame count (TIMI FC) as the reference standard of microvascular assessment; and their relationship with infarct size and ventricular function., Methods: First-pass perfusion and late gadolinium enhancement imaging were performed in 25 consecutive AMI patients (84% men, age 58 +/- 10) within 72 h of successful reperfusion. We assessed the myocardial extent of microvascular dysfunction using the size of the perfusion defect on first-pass perfusion (PD%) and the hypoenhanced core region within late gadolinium enhancement (MDEcore%). PD%, MDEcore%, and TIMI FC were analyzed independently of each other and with blinding to clinical data. We adjusted PD% and MDEcore% to the myocardial mass subtended by the infarct-related artery according to the 16-segment model., Results: Median infarct size involved 13.9% (interquartile range: 8.5 to 22.2%) of the left ventricle and median left ventricular ejection fraction was 52% (interquartile range: 43 to 61%). PD% demonstrated evidence of microvascular dysfunction more frequently (84% vs. 36% of patients, p < 0.002) and involved a larger myocardial extent (23.5 +/- 17.5% vs. 3.5 +/- 7.7%, p < 0.001) compared to MDEcore%. PD% had strong correlations with TIMI FC (Spearman rho = 0.62, p < 0.001) and infarct size (rho = 0.64, p < 0.001), and a moderate correlation with LVEF (rho = -0.39, p = 0.055). MDEcore% also correlated with TIMI FC (rho = 0.54, p = 0.005) and infarct size (rho = 0.52, p < 0.01) but not with LVEF (p = NS)., Conclusions: PD% appeared to provide a stronger noninvasive assessment of the microvascular function than MDEcore% and correlated well with prognostic markers such as left ventricular ejection fraction and infarct size. Future studies should consider quantitative analyses of both first-pass perfusion and late gadolinium enhancement imaging in the evaluation of novel therapies targeted to the microvasculature of the infarct-related artery.

Background: Myocardial performance index (MPI) is a noninvasive, quantitative Doppler measure of global cardiac function, integrating systolic and diastolic functions. The prognostic significance of MPI is less clear for cardiovascular (CV) events after myocardial infarction (MI) among individuals at high risk with depressed left ventricular (LV) systolic function., Methods: We analyzed echocardiograms from 512 patients with depressed LV function after MI enrolled in the Survival and Ventricular Enlargement (SAVE) echocardiographic substudy. Baseline MPI measures were obtainable in 226 patients. The cohort was separated by median MPI (0.50). MPI was related to baseline clinical and echocardiographic characteristics, ventricular remodeling, and subsequent CV events, including recurrent MI, heart failure, CV death, and a composite of all CV end points., Results: An MPI of 0.5 or more was associated with larger infarct size and reduced LV systolic function at baseline; other baseline characteristics between the groups were similar. A total of 64 (28.3%) patients experienced CV events. Baseline MPI did not influence ventricular remodeling and did not modify the relationship between ventricular dilatation and CV events. After covariate adjustment, an MPI of 0.50 or higher remained an independent predictor for adverse CV events (hazard ratio [HR], 2.00, 95% confidence interval 1.17-3.43)., Conclusions: An MPI of 0.50 or greater is an independent predictor for CV events after MI in patients with known LV dysfunction.

Heart failure (HF) is a clinical syndrome that occurs when the ability of the heart to meet the requirements of the body fails. Myocardial infarction (MI) is a common antecedent event that predisposes a patient to HF. Loss of cardiac function following MI occurs in the context of myocyte death and ventricular remodeling. The clinical significance of HF following MI is underscored by the fact that among MI survivors, the risk of death is markedly elevated in those who develop HF compared with those who do not. Various modifying factors associated with the development of HF following MI have been identified. Use of multimodality therapy with improved clinical outcomes for HF has increased the need to specifically identify the failing heart at an earlier stage. The ability to identify heart failure early in its pathogenesis will enable finer risk stratification following MI. This article reviews various risk predictors for the development of HF following MI.

Background: Angiotensin-converting enzyme (ACE) inhibitors have been shown to attenuate left ventricular (LV) enlargement in association with reducing mortality after myocardial infarction (MI). Preclinical data suggest that angiotensin receptor blockers (ARBs) may have similar structural and functional effects after MI. The Valsartan in Acute Myocardial Infarction (VALIANT) Echo study was designed to test the hypothesis that the ARB valsartan, either alone or in combination with captopril, could attenuate progressive LV enlargement or improve LV ejection fraction to a greater extent than captopril alone., Methods and Results: Six hundred ten patients enrolled in the main VALIANT study who experienced MI and evidence of LV dysfunction, heart failure, or both were enrolled in the VALIANT Echo study. Patients were randomized to receive valsartan 160 mg PO BID, captopril 50 mg PO TID, or valsartan 80 mg PO BID plus captopril 50 mg PO TID between 1 and 10 days after MI. Six hundred three patients had echocardiograms of sufficient quality for quantitative analysis. Echocardiograms were digitized, and endocardial borders were traced manually from 2 short-axis and 2 apical views. Ventricular volumes, ejection fractions, combined areas, and infarct segment length were measured, and changes in echocardiographic measures from baseline to 20 months were compared between treatment groups. Baseline clinical and echocardiographic characteristics were similar in the 3 treatment arms. The changes from baseline to 20 months in all echocardiographic parameters were similar in all 3 treatment arms. Baseline echocardiographic measures of ejection fraction, end-diastolic volume, and infarct segment length were highly predictive of outcomes including total mortality, death or hospitalization for heart failure, or death or any cardiovascular event (heart failure, MI, stroke, resuscitated sudden death), even after adjustment for known covariates., Conclusions: Treatment with the ACE inhibitor captopril, valsartan, or the combination of captopril plus valsartan resulted in similar changes in cardiac volume, ejection fraction, and infarct segment length between baseline and 20 months after MI. Baseline echocardiographic measures were powerfully and independently predictive of all major outcomes.

Cardiac remodelling is the expression of molecular, cellular and interstitial changes in response to cardiac injury, manifesting as adverse alterations in the size, shape and function of the ventricle. Several clinical studies have documented significant elevations in the levels of renin, angiotensin II (Ang II) and aldosterone attending acute myocardial infarction and/or congestive heart failure. Similar to catecholamines, markedly elevated activity of the renin-angiotensin-aldosterone system (RAAS) is associated with poor prognosis. The effects of Ang II upon cardiac tissue are related to two primary receptors, Ang II type 1 (AT1) and Ang II type 2 (AT2). The AT1-receptor appears to mediate many of the deleterious effects of chronic RAAS activity, while the AT2-receptor is increasingly shown to have potential cardioprotective effects. Attenuating the deleterious effects of sustained Ang II stimulation can be achieved by direct inhibition of angiotensin- converting enzyme (ACE) and/or direct antagonism of AT receptors. ACE inhibition reduces left ventricular (LV) volumes, retards the progression of LV dilatation and hypertrophy and increases systolic function in systolic dysfunction. By blocking at the receptor level, Ang II receptor blockers (ARBs) provide an alternative and more direct approach to inhibiting the effects of Ang II; however, data relating to their effects upon ventricular remodelling, whether used in isolation or in combination with ACE inhibitors (ACE-Is), are less convincing. Data arising from several recent clinical trials suggest that simultaneous use of ACE-Is and ARBs maybe of more benefit in attenuating ventricular remodelling than either agent alone.

National Kidney Foundation guidelines define chronic kidney disease (CKD) as persistent kidney damage (confirmed by renal biopsy or markers of kidney damage) and/or glomerular filtration rate (GFR) <60 mL/min/1.73m2 for greater than three months. Patients with CKD experience higher mortality and adverse cardiovascular (CV) event rates, which remains significant after adjustment for conventional coronary risk factors. This progressive CV risk associated with worsening renal function may be explained by other factors that become increasingly important with renal decline. In this regard, more investigation of nonconventional factors that have received a lot of attention includes associations with inflammation, albuminuria, reduced vascular compliance, and homocysteine. In addition, individuals with CKD encounter the problem of "therapeutic nihilism," in which there is a lack of appropriate risk factor modification and intervention, despite established awareness of their high cardiovascular risk. Several studies suggest that these individuals derive as much, if not more, benefit from evidence-based cardiovascular therapies and strategies. Greater educational efforts are needed to reduce this therapeutic gap.

Individuals with type 2 diabetes and nephropathy represent a particularly high-risk group for both adverse cardiac as well as renal events. Using the Irbesartan in Diabetic Nephropathy Trial (IDNT) cohort, our objective was to determine baseline characteristics of individuals with type 2 diabetic nephropathy and hypertension predictive for cardiac events. IDNT identified 1715 individuals with type 2 diabetic nephropathy and hypertension having serum creatinine of 1.0 to 3.0 mg/dL and urinary albumin excretion rates > or = 900 mg/day. A cardiovascular (CV) composite was used consisting of CV death, nonfatal MI, hospitalization for heart failure, stroke, amputation, and coronary and peripheral revascularization. Using multivariable Cox regression analysis, 41 baseline characteristics determined a priori were analyzed for their potential relationship to risk of experiencing a CV event. Of the 1715 individuals, 518 (30.2%) had at least one of the CV composite end points. Older age, male gender, longer duration of diabetes, history of cardiovascular disease, history of CHF, high urinary albumin:creatinine ratio, and low serum albumin were strong predictors for CV events; of these, prior history of CVD (RR 2.00, 95% CI 1.63-2.45; P < 0.0001) and high urinary albumin:creatinine ratio (RR 1.29 per natural log unit, 95% CI 1.13-1.48; P = 0.0002) at baseline were highly predictive for cardiovascular events. In conclusion, among individuals with hypertension and diabetic nephropathy, both the degree of albuminuria and lower serum albumin levels provide additional prognostic information concerning cardiovascular risk, in addition to traditional coronary risk factors.

Background: The presence of coexisting conditions has a substantial effect on the outcome of acute myocardial infarction. Renal failure is associated with one of the highest risks, but the influence of milder degrees of renal impairment is less well defined., Methods: As part of the Valsartan in Acute Myocardial Infarction Trial (VALIANT), we identified 14,527 patients with acute myocardial infarction complicated by clinical or radiologic signs of heart failure, left ventricular dysfunction, or both, and a documented serum creatinine measurement. Patients were randomly assigned to receive captopril, valsartan, or both. The glomerular filtration rate (GFR) was estimated by means of the four-component Modification of Diet in Renal Disease equation, and the patients were grouped according to their estimated GFR. We used a 70-candidate variable model to adjust and compare overall mortality and composite cardiovascular events among four GFR groups., Results: The distribution of estimated GFR was wide and normally shaped, with a mean (+/-SD) value of 70+/-21 ml per minute per 1.73 m2 of body-surface area. The prevalence of coexisting risk factors, prior cardiovascular disease, and a Killip class of more than I was greatest among patients with a reduced estimated GFR (less than 45.0 ml per minute per 1.73 m2), and the use of aspirin, beta-blockers, statins, or coronary-revascularization procedures was lowest in this group. The risk of death or the composite end point of death from cardiovascular causes, reinfarction, congestive heart failure, stroke, or resuscitation after cardiac arrest increased with declining estimated GFRs. Although the rate of renal events increased with declining estimated GFRs, the adverse outcomes were predominantly cardiovascular. Below 81.0 ml per minute per 1.73 m2, each reduction of the estimated GFR by 10 units was associated with a hazard ratio for death and nonfatal cardiovascular outcomes of 1.10 (95 percent confidence interval, 1.08 to 1.12), which was independent of the treatment assignment., Conclusions: Even mild renal disease, as assessed by the estimated GFR, should be considered a major risk factor for cardiovascular complications after a myocardial infarction., (Copyright 2004 Massachusetts Medical Society)

Objectives: To investigate the hypothesis that prior angina pectoris confers protection from remodeling occurring after myocardial infarction (MI), we analyzed echocardiograms from the Healing and Early Afterload Reducing Therapy (HEART) trial., Background: Ischemia occurring before MI has been shown to reduce infarct size in experimental models and to improve outcomes in patients. The extent to which ischemia occurring before MI influences subsequent changes in ventricular size and function is unclear., Methods: We studied 283 patients enrolled in the HEART trial who had echocardiograms at days 1 and 90 after MI. Left ventricular (LV) dilation from days 1 to 90 was used as a measure of LV remodeling. We explored the relationship between symptomatic angina occurring before infarction and subsequent LV remodeling., Results: In patients who reported angina (n = 111) during the three months preceding MI, LV volume change was -0.73 +/- 2.6 ml over the 90-day post-MI period, compared with 6.8 +/- 2.6 ml for patients (n = 172) without angina (p = 0.017). In contrast, there were no differences in changes in ejection fraction based on prior angina. Maximal creatine kinase was significantly lower in patients with prior angina (2,119 +/- 1,729 vs. 2,701 +/- 2,088, p = 0.016). In a multivariate model, prior angina remained protective for ventricular remodeling after adjusting for age, gender, baseline ejection fraction, Killip class, baseline end-diastolic volume, and drug treatment group (p = 0.042). However, the protective effect of pre-infarction angina appeared to be attenuated in diabetic patients., Conclusions: Ischemic symptoms occurring before MI may protect against LV remodeling. These protective effects may be secondary to recruitment of collaterals or ischemic preconditioning of the myocardium, and they appear to be attenuated in diabetic patients.

The synthesis of S-(-)-1-(4-(2-ethoxyethoxy)phenoxy)-2-hydroxy-3-(2-(3,4-dimethoxyphenyl)ethylamino)propane hydrochloride (D140S.HCl 6), a novel short acting beta(1)-specific adrenoceptor antagonist, has been described. The antagonist potency for D140S.HCl 6 has been compared with esmolol, another short acting agent, and other well known beta-adrenoceptor antagonists in isolated rat tissue preparations. The pharmacokinetics of D140S.HCl 6 in 7 day continuous intravenous infusions and 4 weeks intravenous bolus injection studies in conscious rats and dogs have been examined in toxicology studies. The effect on the isoprenaline-induced heart rate increase and the pharmacodynamic half-life of D140S.HCl 6 has been compared with esmolol in a conscious rat model. In addition, the results of a range of toxicological studies are presented. The results indicate that D140S.HCl 6 is a highly specific beta(1)-adrenoceptor antagonist (pA(2) = 8.15+/-0.22, beta(1)/beta(2) selectivity > 4400). The in vitro studies suggest D140S.HCl is ca. ten times more potent and 60 times more beta(1)-specific than racemic esmolol. Pharmacokinetic non-linearity was seen when given as a 7 day intravenous infusion at toxicological doses above 10 mg kg(-1) h(-1) in the rat and 2.5 mg kg(-1) h(-1) in the dog. Both D140S.HCl 6 and esmolol have very short durations of action after intravenous infusion in the rat (pharmacodynamic half-life is < 15 min for D140S.HCl and 10 min for esmolol). The toxicological tests indicate that D140S.HCl 6 shows no unexpected toxicity and none of the tissue irritancy problems reported for esmolol formulations., (Copyright 2002 Editions scienctifiques et médicales Elsevier SAS)