Angiotensin-Neprilysin Inhibition and Renal Outcomes in Heart Failure With Preserved Ejection Fraction.

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).

Shortness of breath in clinical practice: A case for left atrial function and exercise stress testing for a comprehensive diastolic heart failure workup.

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.

Giant coronary aneurysm presenting as a cardiac mass on transthoracic echocardiogram.

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.

Comorbid Heart Failure and Renal Impairment: Epidemiology and Management.

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.

The cardiorenal syndrome.

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.

Comparison of renal function and cardiovascular risk following acute myocardial infarction in patients with and without diabetes mellitus.

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.

Usefulness of right ventricular fractional area change to predict death, heart failure, and stroke following myocardial infarction (from the VALIANT ECHO Study).

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.

The relationship between renal function and cardiac structure, function, and prognosis after myocardial infarction: the VALIANT Echo Study.

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.

Two-dimensional assessment of right ventricular function: an echocardiographic-MRI correlative study.

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.

Impact of prior antiplatelet therapy on risk of embolism in infective endocarditis.

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.

Comparison of regional versus global assessment of left ventricular function in patients with left ventricular dysfunction, heart failure, or both after myocardial infarction: the valsartan in acute myocardial infarction echocardiographic study.

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.

Characterization of microvascular dysfunction after acute myocardial infarction by cardiovascular magnetic resonance first-pass perfusion and late gadolinium enhancement imaging.

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.

Risk assessment in patients with depressed left ventricular function after myocardial infarction using the myocardial performance index--Survival and Ventricular Enlargement (SAVE) experience.

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.

Clinical modifiers for heart failure following myocardial infarction.

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.

Angiotensin II receptor blockade and ventricular remodelling.

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.

Changes in ventricular size and function in patients treated with valsartan, captopril, or both after myocardial infarction.

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.

Predictors of cardiovascular events in patients with type 2 diabetic nephropathy and hypertension: a case for albuminuria.

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.

Cardiovascular risk in chronic kidney disease.

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.

Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction.

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.

Angina pectoris prior to myocardial infarction protects against subsequent left ventricular remodeling.

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.

Synthesis, beta-adrenoceptor pharmacology and toxicology of S-(-)-1-(4-(2-ethoxyethoxy)phenoxy)-2-hydroxy-3-(2-(3,4-dimethoxyphenyl)ethylamino)propane hydrochloride, a short acting beta(1)-specific antagonist.

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.