Sumant Lamba

B-type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure: analysis from Breathing Not Properly (BNP) Multinational Study.

Background—We sought to determine the degree to which B-type natriuretic peptide (BNP) adds to clinical judgment in the diagnosis of congestive heart failure (CHF). Methods and Results—The Breathing Not Properly Multinational Study was a prospective diagnostic test evaluation study conducted in 7 centers. Of 1586 participants who presented with acute dyspnea, 1538 (97%) had clinical certainty of CHF determined by the attending physician in the emergency department. Participants underwent routine care and had BNP measured in a blinded fashion. The reference standard for CHF was adjudicated by 2 independent cardiologists, also blinded to BNP results. The final diagnosis was CHF in 722 (47%) participants. At an 80% cutoff level of certainty of CHF, clinical judgment had a sensitivity of 49% and specificity of 96%. At 100 pg/mL, BNP had a sensitivity of 90% and specificity of 73%. In determining the correct diagnosis (CHF versus no CHF), adding BNP to clinical judgment would have enhanced diagnostic accuracy from 74% to 81%. In those participants with an intermediate (21% to 79%) probability of CHF, BNP at a cutoff of 100 pg/mL correctly classified 74% of the cases. The areas under the receiver operating characteristic curve were 0.86 (95% CI 0.84 to 0.88), 0.90 (95% CI 0.88 to 0.91), and 0.93 (95% CI 0.92 to 0.94) for clinical judgment, for BNP at a cutoff of 100 pg/mL, and for the 2 in combination, respectively (P <0.0001 for all pairwise comparisons). Conclusions—The evaluation of acute dyspnea would be improved with the addition of BNP testing to clinical judgment in the emergency department.

Alterations in adrenergic receptor signaling in heart failure.

In the failing heart, several changes occur in cardiac adrenergic receptor-signal transduction pathways. The most striking of these changes occur in β-ARs, and of the changes in β-adrenergic receptors, β1-receptor down-regulation is the most prominent. Other changes include uncoupling of β2-adrenergic receptors and increased activity of the inhibitory G-protein, Gi. Most of these changes appear to be related to increased activity of the adrenergic nervous system, i.e. increased exposure to norepinephrine. Antagonists of the adrenergic nervous system improve left ventricular function and outcome in patients with heart failure. This fact supports the notion that activation of these neurohormonal systems exerts a net long-term detrimental effect on the natural history of chronic heart failure and that myocardial adrenergic desensitization phenomena are at least partially adaptive in the setting of left ventricular dysfunction.

What causes elevated B-type natriuretic peptide in patients without heart failure?

Background. Hypertension (HTN) and high serum cholesterol (HC) level are often combined in the same subject where they contribute to the overall cardiovascular risk proflle. HC is associated with a” impaired vasodilatory capacity and a” overexpression of vascular angiotensin II receptors, which can contribute to the develpment of HTN. Aim of the present study was to investigate the role of HC, if any, in the development of HTN in the Brisighella Heart Study. Methods. 1230 “ormotensive subjects (SBP/DBPcl40/90 mmHg) enrolled in the Brislghella Heart Study in 1972 have been divided according to total serum cholesterol (TChol) tertiles and followed for 12 years to evaluate the proportion of patients developing HTN defined as SBP and/or DBP>l40/90 mmHg and/or therapy for HTN. Results. After adjustment for the main counfondlng factors (family history of HTN, age, BMI, sex, diabetes) the rate of HTN was significantly increased in subjects with T-Chol z 239 mg/dl both after 8 (1980) and 12 (1984) years of follow-up (‘p<O.OOi YS. other subgroups). The rate of development of HTN was enhanced in the two older subgroups of subjects (30-59 and z-59 years). Conclusion. These data suggest that HC could substantially contribute to the development of HTN and strongly support the wide role of lipid lowering drugs and particulary statins in the pnmary prevention of cardiovascular disease.