Diagnostic accuracy of Doppler echocardiography for determining left ventricular diastolic pressure elevation: prospective comparison to chest radiography, serum B-type natriuretic peptide, and chest auscultation.

BACKGROUND: Doppler echocardiography (DE), chest radiography (CXR), serum B-type natriuretic peptide (BNP) measurement and physical examination are all commonly employed to estimate left ventricular diastolic pressure (LVDP) in clinical care. There are no published studies directly comparing the diagnostic accuracy of these tests. METHODS AND RESULTS: DE, BNP, CXR, and physical examination were performed on 56 consecutive patients immediately following clinically indicated cardiac catheterization with measurement of LVDP. LVDP measured preceding atrial contraction at end-expiration was elevated (>16 mmHg) in 19 subjects. Diagnostic accuracies were 79%, 70%, 61% for DE, BNP, and CXR, respectively. None of the study subjects had evidence of raised LVDP by chest auscultation. CONCLUSIONS: The diagnostic accuracy of DE compares favorably to other noninvasive markers for prediction of invasively determined LVDP.

Severe left ventricular systolic dysfunction increases atrial fibrillation after ablation of atrial flutter.

BACKGROUND: Atrial fibrillation (Afib) that occurs after a successful atrial flutter (AFL) ablation may negate the potential benefits of the ablation. Afib occurs more often when severe left ventricular systolic dysfunction (LVSD) is present. We hypothesized that even after a successful AFL ablation, the incidence of postablation Afib is increased when severe LVSD is present. METHODS: Ninety consecutive patients with LVSD who underwent ablation for AFL at Montefiore Medical Center from August 2001 to January 2005 were classified according to the severity of LVSD. Group 1 (n = 36) consisted of patients with EF < or = 35%, and group 2 (n = 54) consisted of patients with EF 36-55%. There were no statistically significant differences in baseline patient characteristics between the two groups. RESULTS: During a mean follow up of 350 days, Afib occurred in 31% (n = 11; 8 with prior history of AFib) in group 1, and 7.4% (n = 4; all with prior history of Afib) in group 2. Cumulative probability of remaining Afib-free in group 1 versus group 2 was 75% versus 96% at 365 days, and 69% versus 91% at 600 days (P = 0.01). A prior history of Afib did not interact with EF when analyzed with a logistic regression analysis. CONCLUSION: After an AFL ablation, the incidence of Afib is increased, and the probability of remaining free of Afib is decreased, when severe LVSD is present, independent of a prior history of Afib. This finding may have implications for optimal patient selection for AFL ablation, and the use of adjunctive therapies.

Long-term effects of carvedilol or metoprolol on left ventricular function in ischemic and nonischemic cardiomyopathy.

Data regarding the effects of beta blockers on left ventricular (LV) function after 12 months are scarce in ischemic and nonischemic cardiomyopathy. Echocardiograms of 72 patients with ischemic and nonischemic cardiomyopathy, who were free of clinical events susceptible to alter LV function while receiving carvedilol or metoprolol for at least 24 months, were prospectively reanalyzed. Twelve months after beta-blocker initiation, LV ejection fraction (EF) increased by > or = 5% in 75% of patients, whereas EF failed to increase by 5% or decreased in the remaining 25%. Over the subsequent 32 months, LVEF increased further in patients who had experienced an initial EF increase by > or = 5%, whereas EF tended to further decrease in patients who had experienced an initial EF increase of <5% or a decrease. Thus, the benefits of carvedilol or metoprolol on LV function are long lasting in patients with ischemic or nonischemic cardiomyopathy who are free of events susceptible to alter LV function while receiving beta blockade.

Endothelial cell activation in patients with decompensated heart failure.

BACKGROUND: Vascular endothelial functions, other than nitric oxide (NO)-mediated control of vasomotor tone, are poorly characterized in patients with chronic heart failure (CHF). Veins and arteries are exposed to the same circulating proinflammatory mediators in patients with CHF. The present study tested whether endothelial cell activation occurs in veins of patients with decompensated CHF and whether activation, if present, subsides with return to a clinically compensated state. METHODS AND RESULTS: Fifteen patients with decompensated CHF requiring transient inotropic support and 6 age-matched, healthy controls were studied. Endothelial cells and blood were collected from a forearm vein, and brachial artery flow-mediated dilation (FMD) was measured before and 24 hours after discontinuation of short-term inotropic therapy, when patients had returned to a steady compensated state. Nitrotyrosine immunoreactivity (an intracellular marker of oxidative stress), cyclooxygenase-2 (COX-2), and inducible NO synthase (iNOS) expression were significantly higher in venous endothelial cells of patients in clinical decompensation when compared with healthy subjects. Return to a compensated state resulted in a significant reduction in nitrotyrosine immunoreactivity, COX-2, and iNOS expression. Concomitantly, a significant increase in FMD and a decline in plasma total 8-isoprostane and bicycloprostaglandin E2 levels were observed. Venous endothelial NOS expression was unaffected by clinical decompensation. CONCLUSIONS: Clinical decompensation in CHF is associated with activation of the venous endothelium. Return to a compensated state after short-term inotropic therapy results in a significant reduction in endothelial nitrotyrosine formation, COX-2, and iNOS expression.

Vasopressin antagonists in heart failure.

The recrudescence of interest in manipulation of the arginine vasopressin system and especially of V2 vasopressin receptor blockade in heart failure stems from the limited efficacy and possible detrimental effects of loop diuretics. The "braking phenomenon," hypertrophy of the collecting duct cells, and altered pharmacodynamics contribute to loop diuretic resistance in heart failure. Selective (tolvaptan) and nonselective (conivaptan) V2 vasopressin receptor antagonists now known as "vaptans" promote free-water excretion that is labeled aquaresis and correct hyponatremia in patients with severe heart failure. A large mortality study with tolvaptan in heart failure is presently ongoing.

Management of diastolic heart failure.

A number of large randomized, placebo-controlled mortality trials provided evidence-based data to guide the treatment of patients with systolic heart failure, but, with one exception, similar trials in patients with diastolic heart failure (DHF) either are not yet completed or have not been conducted at all. However, randomized outcomes trials conducted in patients with hypertension with and without left ventricular hypertrophy and in patients with vascular diseases at high risk for cardiovascular events provide a strong rationale for long-term angiotensin-converting enzyme inhibition or angiotensin receptor blockade in patients with DHF. The treatment of patients with acutely decompensated DHF remains purely empirical. Thus, a pragmatic approach to the treatment of acutely decompensated DHF that includes the use of B-type natriuretic peptide is presented.

Evolving rationale for angiotensin-converting enzyme inhibition in chronic heart failure.

The rationale behind the use of angiotensin-converting enzyme (ACE) inhibitors has evolved considerably since their approval for the treatment of hypertension. The initial rationale behind their use for the treatment of chronic heart failure was to duplicate with one agent the hemodynamic effects produced by the hydralazine-isosorbide dinitrate combination, i.e., increasing cardiac output while reducing ventricular filling pressures. The observation that the acute hemodynamic effects of ACE inhibitors did not predict long-term clinical benefits led to the search for mechanisms other than hemodynamic improvement. Attenuation or even reversal of left ventricular dilatation after myocardial infarction, which was first reported with ACE inhibition in an experimental model of myocardial infarction and subsequently in patients with recent myocardial infarction, provided a new rationale for the use of these inhibitors for chronic heart failure. However, this apparent prevention of left ventricular dilatation by ACE inhibitors is less apparent in patients with congestive heart failure due to left ventricular systolic dysfunction (decreased ejection fraction) than in patients with recent myocardial infarction. Furthermore, the unexpected finding that long-term ACE inhibition decreases the incidence of recurrent myocardial infarction in patients with coronary artery disease and an already reduced systolic function, suggested the hypothesis that vascular protection may provide most of the clinical benefits of ACE inhibitors. This hypothesis was successfully tested by demonstrating a lower incidence of cardiovascular events in high-risk vascular patients randomized to long-term ACE inhibition with ramipril. Accordingly, the current rationale behind the use of ACE inhibitors in patients with chronic heart failure is largely that of vascular protection.

Biopsy coupled to quantitative immunofluorescence: a new method to study the human vascular endothelium.

Limited availability of endothelial tissue is a major constraint when investigating the cellular mechanisms of endothelial dysfunction in patients with metabolic and cardiovascular diseases. We propose a novel approach that combines collection of 200-1,000 endothelial cells from a superficial forearm vein or the radial artery, with reliable measurements of protein expression by quantitative immunofluorescence analysis. This method was validated against immunoblot analysis in cultured endothelial cells. Levels of vascular endothelial cell activation, oxidative stress, and nitric oxide synthase expression were measured and compared in five patients with severe chronic heart failure and in four healthy age-matched subjects. In summary, vascular endothelial biopsy coupled with measurement of protein expression by quantitative immunofluorescence analysis provides a novel approach to the study of the vascular endothelium in humans.