Hemodynamic comparison of restrictive mitral valve annuloplasty and mitral valve replacement for ischemic mitral regurgitation

in Circulation (2013)

Exercise pulmonary hypertension in asymptomatic degenerative mitral regurgitation

in Circulation (2010), 122(1), 33-41

BACKGROUND: Current guidelines recommend mitral valve surgery for asymptomatic patients with severe degenerative mitral regurgitation and preserved left ventricular systolic function when exercise ... [more ▼]

BACKGROUND: Current guidelines recommend mitral valve surgery for asymptomatic patients with severe degenerative mitral regurgitation and preserved left ventricular systolic function when exercise pulmonary hypertension (PHT) is present. However, the determinants of exercise PHT have not been evaluated. The aim of this study was to identify the echocardiographic predictors of exercise PHT and the impact on symptoms. <br /> <br />METHODS AND RESULTS: Comprehensive resting and exercise transthoracic echocardiography was performed in 78 consecutive patients (age, 61+/-13 years; 56% men) with at least moderate degenerative mitral regurgitation (effective regurgitant orifice area =43+/-20 mm(2); regurgitant volume =71+/-27 mL). Exercise PHT was defined as a systolic pulmonary arterial pressure (SPAP) >60 mm Hg. Exercise PHT was present in 46% patients. In multivariable analysis, exercise effective regurgitant orifice was an independent determinant of exercise SPAP (P<0.0001) and exercise PHT (P=0.002). Resting PHT and exercise PHT were associated with markedly reduced 2-year symptom-free survival (36+/-14% versus 59+/-7%, P=0.04; 35+/-8% versus 75+/-7%, P<0.0001). After adjustment, although the impact of resting PHT was no longer significant, exercise PHT was identified as an independent predictor of the occurrence of symptoms (hazard ratio=3.4; P=0.002). Receiver-operating characteristics curves revealed that exercise PHT (SPAP >56 mm Hg) was more accurate than resting PHT (SPAP >36 mm Hg) in predicting the occurrence of symptoms during follow-up (P=0.032). <br /> <br />CONCLUSIONS: Exercise PHT is frequent in patients with asymptomatic degenerative mitral regurgitation. Exercise mitral regurgitation severity is a strong independent predictor of both exercise SPAP and exercise PHT. Exercise PHT is associated with markedly low 2-year symptom-free survival, emphasizing the use of exercise echocardiography. An exercise SPAP >56 mm Hg accurately predicts the occurrence of symptoms. [less ▲]

Risk Score for Predicting Outcome in Patients With Asymptomatic Aortic Stenosis

in Circulation (2009), 120(1), 69-75

Background— The management of patients with asymptomatic severe aortic stenosis remains controversial. We sought to develop a continuous risk score for predicting the midterm development of symptoms or ... [more ▼]

Background— The management of patients with asymptomatic severe aortic stenosis remains controversial. We sought to develop a continuous risk score for predicting the midterm development of symptoms or adverse events in this setting. Methods and Results— We prospectively followed 107 patients with asymptomatic aortic stenosis (aged 72 years [63 to 77]; 35 women; aortic-jet velocity, 4.1 m/s [3.5 to 4.4]) at a single center in France. Predefined end points for assessing outcome were the occurrence within 24 months of death or aortic valve replacement necessitated by symptoms or by a positive exercise test. Variables independently associated with outcome were used to build a score that was validated in an independent cohort of 107 patients from Belgium. Independent predictors of outcome were female sex, peak aortic-jet velocity, and B-type natriuretic peptide at baseline. Accordingly, the score could be calculated as follows: Score=[peak velocity (m/s)x2]+(natural logarithm of B-type natriuretic peptidex1.5)+1.5 (if female sex). Event-free survival after 20 months was 80% for patients within the first score quartile compared with only 7% for the fourth quartile. Areas under the receiver operating characteristic curve for the score were 0.90 and 0.89 in the development and validation cohorts, respectively. Conclusions— If further validation is achieved, this score may be useful to predict outcome in individual patients with asymptomatic aortic stenosis to select those who might benefit from early surgery. [less ▲]

Predictors of outcomes in low-flow, low-gradient aortic stenosis: results of the multicenter TOPAS Study.

in Circulation (2008), 118(14 Suppl), 234-242

Preoperative posterior leaflet angle accurately predicts outcome after restrictive mitral valve annuloplasty for ischemic mitral regurgitation

in Circulation (2007), 115(6), 782-791

Evidence for HLA-DQA1 locus being associated with abdominal aortic aneurysms in the Belgian population

in Circulation (2005, April 12), 111(14), 219

Cardiomyocyte-restricted overexpression of endothelial nitric oxide synthase (NOS3) attenuates beta-adrenergic stimulation and reinforces vagal inhibition of cardiac contraction.

in Circulation (2004), 110(17), 2666-72

BACKGROUND: In the heart, nitric oxide synthases (NOS) modulate cardiac contraction in an isoform-specific manner, which is critically dependent on their cellular and subcellular localization. Defective ... [more ▼]

BACKGROUND: In the heart, nitric oxide synthases (NOS) modulate cardiac contraction in an isoform-specific manner, which is critically dependent on their cellular and subcellular localization. Defective NO production by NOS3 (endothelial NOS [eNOS]) in the failing heart may precipitate cardiac failure, which could be reversed by overexpression of NOS3 in the myocardium. METHODS AND RESULTS: We studied the influence of NOS3 in relation to its subcellular localization on the function of cardiomyocytes isolated from transgenic mice overexpressing NOS3 under the alpha-myosin heavy chain promoter (NOS3-TG). Immunoblot analysis demonstrated moderate (5-fold) NOS3 overexpression in cardiomyocytes from NOS3-TG heterozygotes. Caveolar localization of transgenic eNOS was demonstrated by immunofluorescence, coimmunoprecipitation with caveolin-3, sucrose gradient fractionation, and immunogold staining revealed by electron microscopy. Compared with wild-type littermate, contractility of NOS3-TG cardiomyocytes analyzed by videomicroscopy revealed a lower incidence of spontaneous arrhythmic contractions (n=32, P<0.001); an attenuation of the beta-adrenergic positive inotropic response (isoproterenol, 10(-7) mol/L: 62.1+/-7.8% versus 90.8+/-8.0% of maximum Ca2+ response; n=10 to 17; P<0.05); a potentiation of the muscarinic negative chronotropic response (carbamylcholine, 3.10(-8) mol/L: -63.9+/-14% versus -27.7+/-5.6% of basal rate; n=8 to 10; P<0.05), confirmed by telemetry in vivo; and an attenuation of the accentuated antagonism of beta-adrenergically stimulated contraction (-14.6+/-1.5% versus -3.5+/-1.5; n=7 to 11; P<0.05). Cardiomyocyte NOS inhibition reversed all 4 effects (P<0.05). CONCLUSIONS: Moderate overexpression of NOS3, targeted to caveolae in murine cardiomyocytes, potentiates the postsynaptic muscarinic response and attenuates the effect of high concentrations of catecholamines. Cardiomyocyte NOS3 may represent a promising therapeutic target to restore the sympathovagal balance and protect the heart against arrhythmia. [less ▲]

Rosuvastatin decreases caveolin-1 and improves nitric oxide-dependent heart rate and blood pressure variability in apolipoprotein E-/- mice in vivo.

in Circulation (2003), 107(19), 2480-6

BACKGROUND: Decreased heart rate variability (HRV) and increased blood pressure variability (BPV), determined in part by nitric oxide (NO)-dependent endothelial dysfunction, are correlated with adverse ... [more ▼]

BACKGROUND: Decreased heart rate variability (HRV) and increased blood pressure variability (BPV), determined in part by nitric oxide (NO)-dependent endothelial dysfunction, are correlated with adverse prognosis in cardiovascular diseases. We examined potential alterations in BPV and HRV in genetically dyslipidemic, apolipoprotein (apo) E-/-, and control mice and the effect of chronic statin treatment on these parameters in relation to their NO synthase (NOS)-modifying properties. METHODS AND RESULTS: BP and HR were recorded in unrestrained, nonanesthetized mice with implanted telemetry devices with or without rosuvastatin. Cardiac and aortic expression of endothelial NOS and caveolin-1 were measured by immunoblotting. Both systolic BP and HR were elevated in apoE-/- mice, with abolition of their circadian cycles. Spectral analysis showed an increase in their systolic BPV in the very-low-frequency (+17%) band and a decrease in HRV in the high-frequency (-57%) band, reflecting neurohumoral and autonomic dysfunction. Decreased sensitivity to acute injection of atropine or an NOS inhibitor indicated basal alterations in both parasympathetic and NOS regulatory systems in apoE-/- mice. Aortic caveolin-1 protein, an inhibitor of endothelial NOS, was also increased in these mice by 2.0-fold and correlated positively with systolic BPV in the very-low-frequency band. Rosuvastatin treatment corrected the hemodynamic and caveolin-1 expression changes despite persisting elevated plasma cholesterol levels. CONCLUSIONS: Rosuvastatin decreases caveolin-1 expression and promotes NOS function in apoE-/-, dyslipidemic mice in vivo, with concurrent improvements in BPV and HRV. This highlights the beneficial effects of rosuvastatin on cardiovascular function beyond those attributed to lipid lowering. [less ▲]

Effect of butorphanol tartrate on shock-related discomfort during internal atrial defibrillation.

in Circulation (1999), 99(14), 1837-42

BACKGROUND: In patients with atrial fibrillation, intracardiac atrial defibrillation causes discomfort. An easily applicable, short-acting analgesic and anxiolytic drug would increase acceptability of ... [more ▼]

BACKGROUND: In patients with atrial fibrillation, intracardiac atrial defibrillation causes discomfort. An easily applicable, short-acting analgesic and anxiolytic drug would increase acceptability of this new treatment mode. METHODS AND RESULTS: In a double-blind, placebo-controlled manner, the effect of intranasal butorphanol, an opioid, was evaluated in 47 patients with the use of a step-up internal atrial defibrillation protocol (stage I). On request, additional butorphanol was administered and the step-up protocol continued (stage II). Thereafter, if necessary, patients were intravenously sedated (stage III). After each shock, the McGill Pain Questionnaire was used to obtain a sensory (S), affective (A), evaluative (E), and total (T) pain rating index (PRI) and a visual analogue scale analyzing pain (VAS-P) and fear (VAS-F). For every patient, the slope of each pain or fear parameter against the shock number was calculated and individual slopes were averaged for the placebo and butorphanol group. All patients were cardioverted at a mean threshold of 4.4+/-3.3 J. Comparing both patient groups for stage II, the mean slopes for PRI-T (P=0.0099), PRI-S (P=0.019), and PRI-E (P=0.015) became significantly lower in the butorphanol group than in the placebo group. Comparing patients who received the same shock intensity ending stage I and going to stage II, in those patients randomized to placebo the mean VAS-P (P=0.023), PRI-T (P=0. 029), PRI-S (P=0.030), and PRI-E (P=0.023) became significantly lower after butorphanol administration. CONCLUSIONS: During a step-up internal atrial defibrillation protocol, intranasal butorphanol decreased or stabilized the value of several pain variables and did not affect fear. Of the 3 qualitative components of pain, only the affective component was not influenced by butorphanol. The PRI evaluated pain more accurately than the VAS. [less ▲]

Thrombolysis in anterior myocardial infarction: effect on regional viability studied with positon emission tomography

in Circulation (1987), 76(suppl.IV), 5