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Inder S Anand

Publications and source records attributed to Inder S Anand.

15 recordsLinked to original sources
PubMed2006

Incremental prognostic value of changes in B-type natriuretic peptide in heart failure.

PURPOSE: B-type natriuretic peptide is one of the most sensitive and specific biohumoral markers of heart failure. We hypothesized that B-type natriuretic peptide changes during treatment of heart failure may provide independent information on disease progression and outcome in patients enrolled in the Val-HeFT trial. METHODS: Patients were divided into four groups according to concentrations of B-type natriuretic peptide at baseline versus 4 months (n = 3740) or 12 months (n = 3343), with respect to the baseline median (97 pg/mL): low-->low (stable below median, 44%-46%), high-->high (stable above median, 32%-37%), high-->low (above to below median, 12%-14%), and low-->high (below to above median, 6%-9%). Cox multivariate regression analysis was used to assess the risk of death and morbidity, with adjustment for baseline B-type natriuretic peptide concentrations. RESULTS: Patients who improved their B-type natriuretic peptide at 4 months (high-->low) had a similar risk for mortality (hazard ratio = 1.191, 95% confidence interval [CI] 0.870-1.631, P =.2746) compared with the low-->low patients. Conversely, patients who worsened in their B-type natriuretic peptide (low-->high) had a risk for mortality (hazard ratio 2.578, CI, 1.861-3.571, P <.0001) higher than patients in the low-->low group, and indistinguishable from the high-->high group. Worsening of B-type natriuretic peptide (low-->high) was associated with 0.03 cm/m2 increase in left ventricular end-diastolic diameter, whereas it decreased by 0.10 cm/m2 in high-->low and low-->low groups (P <.001). CONCLUSIONS: Changes in B-type natriuretic peptide over time with respect to a threshold value of 97 pg/mL convey an independent and additional prognostic value compared with a single determination of B-type natriuretic peptide in a large population of patients with chronic symptomatic heart failure and might be helpful in the management of these patients.

Aged↗
PubMed2005

Chronic heart failure with preserved left ventricular ejection fraction: diagnostic and prognostic value of left atrial size.

BACKGROUND: Almost 40% of patients with heart failure (HF) have preserved left ventricular (LV) ejection fraction (EF) and prognosis similar to those with reduced EF. Data on prognostic markers in such patients are limited. We analyzed the prevalence and prognostic value of left atrial (LA) size in this condition. METHODS: 89 normal subjects (Group I), 38 asymptomatic hypertensive patients (Group II) and 183 HF patients with preserved EF (EF >45%) (Group III) were studied. LA diameter (LAD), LV diastolic (LVD) and systolic (LVS) dimensions and mass (LVmass) and EF were measured. E and A wave velocities and E/A were measured. The primary end point was all cause mortality in group III patients. RESULTS: Groups did not differ in age, gender or EF. Group III patients had larger LAD (4.6+-1.0 cm) compared with both Group I (3.7+/-0.6) and Group II (3.7+/-0.5 cm) (p<0.0001). A markedly enlarged (arbitrarily defined as LAD higher or equal 5 cm) had an odds ratio of 34 (95% CI 8-144) in distinguishing HF patients from normals. After a mean follow-up period of 29+/-27 months, 40 patients (21.9%) died. In Cox univariate analysis, NYHA class (HR 2.8 95% C.I. 1.8-4.3; p<0.0001), diastolic blood pressure (DBP) (HR 0.92 95% C.I. 0.88-0.96; p<0.0001), age (HR 1.059 95% C.I. 1.01-1.11; p=0.02) and LAD (HR 1.72 95% C.I. 1.27-2.3; p=0.0005) were predictors of mortality. LAD predicted survival independently of other variables. CONCLUSION: The left atrium is frequently dilated in HF patients compared with controls despite similar EF. LAD showed powerful prognostic value independent of clinical variables.

Aged↗
PubMed2005

C-reactive protein in heart failure: prognostic value and the effect of valsartan.

BACKGROUND: The role of C-reactive protein (CRP) in heart failure is not well studied. We assessed the prognostic value of CRP in patients randomized in Val-HeFT (Valsartan Heart Failure Trial) and studied changes in CRP that were associated with valsartan. METHODS AND RESULTS: Characteristics of patients with baseline CRP levels above and below the median value were compared. Univariable and multivariable Cox proportional hazards regression models were used to examine the relationship of CRP to mortality and morbidity. Interactions were tested to determine whether differences in CRP changes from baseline to 4 and 12 months between groups randomly assigned to valsartan or placebo depended on baseline ACE inhibitor use. Median plasma CRP was 3.23 mg/L (interquartile range 1.42 to 7.56 mg/L), which is higher than in the general population. Patients with CRP above the median had features of more severe heart failure than those with CRP levels below the median. The cumulative likelihood of death and first morbid event increased with increasing quartile of CRP. Relative to the lowest CRP quartile, the risk of mortality (hazard ratio 1.51, 95% CI 1.2 to 1.9) and first morbid event (hazard ratio 1.53, 95% CI 1.28 to 1.84) was increased in the highest CRP quartile in multivariable models. CRP added incremental prognostic information to that provided by brain natriuretic peptide alone. CRP did not change significantly over time in the placebo group; however, after 12 months, valsartan was associated with a decrease in CRP in patients not receiving ACE inhibitors but not in those receiving ACE inhibitors at 12 months. CONCLUSIONS: CRP is increased in heart failure. Higher levels are associated with features of more severe heart failure and are independently associated with mortality and morbidity. The ability of treatments to reduce CRP levels and the prognostic importance of reducing CRP require further study.

Aged↗
PubMed2005

Anemia and change in hemoglobin over time related to mortality and morbidity in patients with chronic heart failure: results from Val-HeFT.

BACKGROUND: Anemia is known to be a prognostic marker for patients with heart failure. However, little is known about the prognostic value of changes in hemoglobin (Hgb) over time or about the causes of anemia. METHODS AND RESULTS: Retrospective analysis of Valsartan Heart Failure Trial data indicated that the quartile of patients with the biggest average decrease in Hgb over 12 months (from 14.2 to 12.6 g/dL) had significantly (P< or =0.01) increased risk of subsequent hospitalization (hazard ratio [HR], 1.47), morbid events (HR, 1.41), and death (HR, 1.6) compared with the quartile that exhibited little change in Hgb over 12 months (from 13.7 to 13.8 g/dL). Increasing Hgb was significantly associated with lower mortality in patients with (HR, 0.78) and without (HR, 0.79) anemia at baseline. Anemia at baseline and the changes in Hgb were independently associated with serum albumin, blood pressure, glomerular filtration rate, B-type natriuretic peptide, and C-reactive protein. Lack of anemia at baseline and increases in Hgb over 12 months were not associated with smaller left ventricular diameters or higher ejection fractions. CONCLUSIONS: Changes in Hgb over 12 months were inversely associated with subsequent risk of mortality and morbidity, independently of the effects of baseline anemia and other important predictors. Several factors were independently related to anemia at baseline and changes in Hgb, suggesting multiple causes of anemia in patients with heart failure. These findings raise important questions about the optimal level of Hgb in patients with moderate to severe heart failure and how to achieve them.

Aged↗
PubMed2005

Pathogenesis of anemia in cardiorenal disease.

The link between chronic heart failure (CHF) and chronic kidney disease (CKD) is well known. Approximately 50% of patients with CHF have some renal dysfunction, and 25% of patients with CKD and serum creatinine levels ranging from 1.5 mg/dL to 6 mg/dL have CHF. The association of CHF with CKD is strong and may contribute to its long-term progression. Anemia is also common in patients with CKD and contributes to increased morbidity and mortality. More recently, anemia has been found to be frequently present in patients with CHF, and its presence is associated with worse long-term CHF outcomes. Thus, anemia, CHF, and CKD may be independently related to one another, and this relationship may have important implications for their management.

Anemia↗
PubMed2004

Critical stenosis of aortic and mitral valves after mediastinal irradiation.

Radiotherapy is used widely in cancer treatment. Mediastinal irradiation is associated with valvular regurgitation; however, stenosis is rare. We present a patient with critical aortic and mitral valve stenosis after mediastinal irradiation and discuss the natural history, treatment, and prognosis of radiation-associated valvular heart disease.

Aortic Valve Stenosis↗
PubMed2004

Is too much neurohormonal blockade harmful?

A number of neurohormones and cytokines are activated in heart failure and their activity is related to the progression of heart failure. Inhibiting the deleterious effects of the activated sympathetic and the renin-angiotensin-aldosterone systems with b-blockers, angiotensin-converting enzyme inhibitors, and aldosterone blockers has been remarkably successful in improving the survival of patients with heart failure. However, inhibition of the other neurohormones and cytokines has not provided the expected incremental benefit, and in some cases has been deleterious, suggesting a ceiling effect of further neurohormonal blockade. This article reviews some of these studies and analyzes the possible causes of these observations.

Angiotensin Receptor Antagonists↗
PubMed2004

Syndromes of subacute mountain sickness.

Two clinical syndromes, acute and chronic mountain sickness, have traditionally been associated with high altitude. Recently, two separate entities of subacute nature have been described in infants and adults. In this paper, we review the published literature on these conditions. Subacute infantile mountain sickness is a condition seen predominantly in Han Chinese infants living in Tibet, although it has been described in other high altitude communities as well. It came into prominence only after the large-scale migration of Chinese population from the low altitude of mainland China to the high altitudes of the Qinghai-Tibetan plateau. The condition is characterized by features of severe hypoxic pulmonary hypertension and heart failure. Pulmonary histology is consistent with muscularization of the pulmonary arterioles, but no intimal proliferation or plexiform lesions are seen. The second syndrome, adult subacute mountain sickness, has been described almost exclusively in Indian soldiers living at extreme altitude for prolonged periods of time. In this condition also, hypoxic pulmonary hypertension appears to be the dominant factor responsible for severe congestive heart failure. Both these conditions have several similarities with brisket disease in cattle; hypoxic pulmonary vasoconstriction plays an important role in the pathogenesis, and removal from high altitude results in complete resolution. Thus, it appears that both these syndromes are human counterparts of brisket disease in cattle.

Adaptation, Physiological↗
PubMed2003

Sustained reduction of aldosterone in response to the angiotensin receptor blocker valsartan in patients with chronic heart failure: results from the Valsartan Heart Failure Trial.

BACKGROUND: Aldosterone has been implicated in the progression of heart failure. The Valsartan Heart Failure Trial (Val-HeFT) provided the first opportunity to examine the long-term effects of an angiotensin receptor blocker on plasma aldosterone levels in patients with NYHA class II through IV heart failure. METHODS AND RESULTS: Plasma aldosterone was measured by radioimmunoassay in core laboratories at baseline and during follow-up in patients assigned to valsartan at a target dose of 160 mg twice daily or placebo. In the placebo group, aldosterone (baseline, 150+/-160 pg/mL, mean+/-SD; n=2025) increased at 4, 12, and 24 months. In the valsartan group, aldosterone (baseline, 137+/-124 pg/mL, mean+/-SD; n=2023) decreased at 4 months and remained suppressed for up to 2 years. At end point (last measurement in each patient), mean aldosterone increased by 17.8+/-3.0 pg/mL (SEM) (11.9%) in the placebo group and decreased by 23.8+/-3.0 pg/mL (SEM) (-17.4%) in the valsartan group (P<0.00001). The effect of valsartan was similar in all subgroups, including those receiving neither ACE inhibitors (ACE-I) nor beta-blockers (BB) at baseline and those receiving concomitant ACE-I or BB. In contrast, outcome effects varied in the 4 subgroups, with a statistically significant reduction in the combined mortality/morbidity end point in those receiving neither neurohormonal inhibitor and an adverse trend in those treated with both drugs. CONCLUSIONS: Valsartan added to background therapy for heart failure produces sustained reduction in plasma aldosterone, consistent with the observed significant reduction in the combined mortality/morbidity end point. A similar reduction in all subgroups based on ACE-I or BB therapy, despite differing clinical outcomes in these subgroups, suggests that aldosterone plasma levels may not be a critical marker of the progression of heart failure.

Aldosterone↗
PubMed2003

Changes in brain natriuretic peptide and norepinephrine over time and mortality and morbidity in the Valsartan Heart Failure Trial (Val-HeFT).

BACKGROUND: Neurohormones are considered markers of heart failure progression. We examined whether changes in brain natriuretic peptide (BNP) and norepinephrine (NE) over time are associated with corresponding changes in mortality and morbidity in the Valsartan Heart Failure Trial. METHODS AND RESULTS: Plasma BNP and NE were measured before randomization and during follow-up in approximately 4300 patients in the Valsartan Heart Failure Trial. The relation between baseline BNP and NE and all-cause mortality and first morbid event (M&M) was analyzed in subgroups, with values above and below the median, and by quartiles. The change and percent change from baseline to 4 and 12 months in BNP and NE were also analyzed by quartiles for subsequent M&M. Risk ratios for M&M were calculated using a Cox proportional hazard model. Risk ratio of M&M for patients with baseline BNP or NE above the median was significantly higher than that for patients with values below the median. Baseline BNP and NE in quartiles also showed a quartile-dependent increase in M&M. BNP had a stronger association with M&M than NE. Patients with the greatest percent decrease in BNP and NE from baseline to 4 and 12 months had the lowest whereas patients with greatest percent increase in BNP and NE had the highest M&M. CONCLUSIONS: Not only are plasma BNP and NE important predictors of heart failure M&M, but changes in these neurohormones over time are associated with corresponding changes in M&M. These data further reinforce their role as significant surrogate markers in HF and underscore the importance of including their measurement in HF trials.

Biomarkers↗
PubMed2003

The role of arginine vasopressin and its receptors in the normal and failing rat heart.

OBJECTIVE: To evaluate the role of arginine vasopressin (AVP) in the normal and post-myocardial infarction (post-MI) hearts, and to investigate whether chronic AVP receptor antagonism can attenuate post-infarct ventricular remodeling. BACKGROUND: A number of neurohormones, like norepinephrine and angiotensin II, have detrimental effects in heart failure (HF) and inhibiting them is beneficial. AVP shares some important properties with these hormones and is activated in HF. However, its role in the syndrome of HF, especially the effect of AVP inhibition, is largely undefined. METHODS AND RESULTS: Effects of AVP-V1a and AVP-V2 receptor stimulation on normal rat cardiomyocyte contractile function, intracellular calcium [Ca2+]i, inositol 3 phosphate (IP3) generation and cell survival were studied. In post-MI rats, AVP receptor function was assessed in cardiomyocytes as well as isolated working hearts. AVP receptor total number (ligand binding) and mRNA levels (RT-PCR) were measured in myocytes. Finally, the effects of chronic AVP-V1a blockade were assessed in post-MI rats using echo and morphometry to measure ventricular remodeling. Normal cardiomyocytes showed a dose-dependent increase in myocyte contractile function, [Ca2+]i, and IP3 generation in response to AVP-V1a receptor stimulation. AVP-V2 agonists had no effect. Cells from MI hearts showed reduced inotropic response to AVP-V1a stimulation. Myocyte AVP-V1a receptor number and receptor mRNA were decreased. Prolonged exposure to AVP reduced cellular viability. However, chronic AVP-V1a blockade did not attenuate structural remodeling or improve function in post-MI hearts. CONCLUSIONS: Isolated adult rat cardiomyocytes bear AVP-V1a receptors that mediate inotropic effects through the IP3 pathway. These receptors are functionally and numerically downregulated in the post-MI remodeled hearts. Despite evidence that AVP is cytotoxic to cells, chronic AVP-V1a receptor blockade does not attenuate post-MI ventricular remodeling in this model. Thus, AVP may not play a major role in the structural progression of HF.

Animals↗
PubMed2002

Surrogate end points in heart failure.

Because of the increasing number of pharmacologic strategies available for treatment of heart failure (HF), the time has come to reassess the adequacy of end points used to evaluate therapeutic efficacy. Interest in the use of surrogate end points in clinical studies is increasing. A surrogate end point is defined as a measurement that can substitute for a true end point for the purpose of comparing specific interventions or treatments in a clinical trial. A true end point is one that is of clinical importance to the patient (e.g., mortality or quality of life), whereas a surrogate end point is one biologically closer to the disease process (e.g., ejection fraction or left ventricular volume in HF). The prime motivation for the use of a surrogate end point concerns the possible reduction in sample size or trial duration. Such reductions have important cost implications and in some cases may influence trial feasibility. Another, perhaps more important, aspect of measuring surrogate end points is that they increase our understanding of the mechanism of action of drugs and thus may help physicians to take a more enlightened approach in managing their patients. In this article we have analyzed the possible potentials of the surrogate end points in clinical studies of patients with chronic HF. Other uses of possible surrogates are discussed, and the limitations in finding true surrogates are mentioned. At this time we conclude there is no well established surrogate in HF.

Biomarkers↗
PubMed2002

Noninvasive assessment of left ventricular remodeling: concepts, techniques, and implications for clinical trials.

BACKGROUND: Over the past decade, our understanding of the cellular and biochemical mechanisms that underlie global changes in ventricular morphology and function has grown enormously. Nevertheless, although the sequence of events that lead to overt changes in the ventricle begin at the cellular level, in living patients we rarely have the opportunity to assess these phenomena as they occur. Thus, to study the process of remodeling in practice and in clinical trials, we have relied on assessments and measurements derived from cardiac imaging tests. METHODS AND RESULTS: Since the initial angiographic based methods for assessing ventricular remodeling in humans, a variety of techniques has been developed that have been used for assessment of ventricular size, shape, and function for both clinical and research studies. As two-dimensional echocardiography has emerged as the predominant noninvasive diagnostic method for clinical use in evaluating left ventricular function, this modality has become the most widely used technique to assess ventricular remodeling. Nevertheless, nuclear techniques that have proven both reliable and highly reproducible have also been used in clinical and research setting and, more recently, cardiac magnetic resonance imaging has offered the potential to obtain extremely high-quality images of the heart at much higher resolution than either of the other techniques. CONCLUSIONS: Each of these techniques carries specific advantages and disadvantages for assessment of remodeling in individual patients and in the context of large-scale clinical trials.

Clinical Trials as Topic↗
PubMed2002

Ventricular remodeling without cellular contractile dysfunction.

BACKGROUND: A number of factors may contribute to progressive left ventricular (LV) remodeling and global LV dysfunction after myocardial damage. Important among these are loss of myocytes from necrosis or apoptosis, changes in the extracellular matrix (ECM), myocyte contractile dysfunction, and the purely geometric or mechanical effects of structural alterations in the LV. Which of these components is more important at a particular stage in the natural history of LV remodeling is unclear. Nor is it known whether global LV dysfunction can occur in the absence of isolated myocyte contractile dysfunction. METHODS AND RESULTS: We studied the natural history of LV remodeling in the rat infarct model to address the question of whether structural alterations in the heart can contribute directly to LV dysfunction or whether the presence of myocyte contractile dysfunction is essential for the development of systolic LV dysfunction. Over 6 weeks, post-MI rats developed progressive LV remodeling and dysfunction, with alterations in several biochemical markers such as a decrease in sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) and an increase in brain natriuretic peptide (BNP) and Na(+)-Ca(2+) exchanger. Myocytes isolated from the remote noninfarcted LV of the remodeled hearts were hypertrophied. Changes in length of the remodeled myocytes correlated well with indices of global LV remodeling. However, no significant defects were seen in any of the contractile or intracellular calcium transient parameters of the remodeled myocytes in the unloaded state, after viscous loading or during increased stimulation frequency. CONCLUSIONS: These data suggest that myocyte hypertrophy may be dissociated from myocyte contractile defect and that global LV systolic dysfunction can occur in the absence of significant myocyte contractile dysfunction. Factors such as loss of muscle mass from necrosis or apoptosis, increased wall stress, and alterations in the ECM may play a more important role early in the natural history of LV remodeling, before myocyte contractile dysfunction has become apparent.

Animals↗