John Skoularigis

Long-term (3-month) effects of a new beta-blocker (nebivolol) on cardiac performance in dilated cardiomyopathy☆

OBJECTIVESnThis study examined the long-term (3-month) effects of nebivolol, a new beta-adrenergic blocking agent, on cardiac performance in patients with dilated cardiomyopathy.nnnBACKGROUNDnSeveral beta-blocking drugs have been reported to have a beneficial hemodynamic effect in patients with dilated cardiomyopathy, but few data obtained in a placebo-controlled randomized study have addressed the mechanisms of improvement.nnnMETHODSnTwenty-four patients with dilated idiopathic (n = 22) or ischemic (n = 2) cardiomyopathy (ejection fraction 0.15 to 0.40) in stable New York Heart Association functional class II or III were entered into a double-blind randomized trial of nebivolol, a new, potent, selective beta 1-antagonist. Exercise time, invasive hemodynamic data (12- and 24-h monitoring) and variables of left ventricular function were examined at baseline and after 3 months of orally administered nebivolol (1 to 5 mg/day, n = 11) or placebo (n = 13).nnnRESULTSnHeart rate decreased (group mean 85 to 71 beats/min vs. 87 to 87 beats/min with placebo) and stroke volume increased significantly (group mean 43 to 55 ml vs. 42 to 43 ml) with nebivolol; decreases in systemic resistance, systemic arterial pressure, wedge pressure and pulmonary artery pressure were not significantly different from those with placebo. Similar hemodynamic results were obtained in the catheterization laboratory. Analysis of high fidelity measurements of left ventricular pressure showed a decrease in left ventricular end-diastolic pressure in the nebivolol group (group mean 21 to 15 vs. 24 to 20 mm Hg with placebo) but no change in the maximal rate of pressure development or in two variables of left ventricular relaxation (maximal negative rate of change of left ventricular pressure [dP/dtmax] and the time constant tau). Left ventricular mass decreased (p = 0.04). Despite a decrease in heart rate with nebivolol, there was a slight decrease in left ventricular end-diastolic volume (p = NS). End-systolic volume tended to decrease (p = 0.07) despite no reduction in end-systolic stress. The net result was a significant increase in ejection fraction (group mean 0.23 to 0.33 vs. 0.21 to 0.23 with placebo), presumably as a result of an increase in contractile performance. This effect was corroborated by an increase in a relatively load-independent variable of myocardial performance.nnnCONCLUSIONSnNebivolol improved stroke volume, ejection fraction and left ventricular end-diastolic pressure, not through a measurable reduction in afterload or a lusitropic effect, but by improving systolic contractile performance.

A case for early surgery in native left-sided endocarditis complicated by heart failure: Results in 203 patients☆

From January 1982 to December 1988, 203 consecutive patients were selected for early valve replacement (mean 10 days from time of admission) if they had clinical evidence of native valve endocarditis with 1) vegetations on echocardiography, 2) severe valvular lesions, and 3) heart failure. Surgery was performed within 7 days of admission in 56% of patients and was done urgently because of hemodynamic deterioration in 108 (53%). All vegetations were identified by echocardiography and confirmed macroscopically at surgery. One hundred ten patients had isolated aortic valve infection, 50 had isolated mitral valve infection (p less than 0.05 for aortic vs. mitral) and 43 had double-valve infection. Mean aortic cross-clamp time was 57, 38 and 67 min, respectively. Sixty-four patients (32%) had extensive infection involving the anulus or adjacent tissues, or both; such infection more frequently involved the aortic than the mitral valve (p less than 0.05). Thirty-eight patients (35%) with aortic valve infection had abscess formation compared with 1 patient (2%) with mitral valve infection (p less than 0.05). Only eight patients (4%) died in the hospital. There were seven patients (3%) with a periprosthetic leak and five patients (3%) with early prosthetic valve endocarditis. Long-term follow-up, available in 174 hospital survivors (89%), revealed 10 deaths and two new ring leaks at 38 +/- 22 months. In conclusion, among patients with endocarditis who need surgery for heart failure, aortic valve infection is more prevalent than mitral valve infection and is more often associated with extensive infection, including abscess formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Frequency and severity of intravascular hemolysis after left-sided cardiac valve replacement with medtronic hall and St. Jude medical prostheses, and influence of prosthetic type, position, size and number

Intravascular hemolysis occurs often in patients with mechanical heart valve prostheses, but in most cases is of mild degree and subclinical. The severity of hemolysis is reported to be related to the type, position and size of prostheses used, as well as the presence of valve malfunction. Hemolysis was evaluated in 170 patients with St. Jude Medical (SJM) and 80 patients with Medtronic Hall (MH) prostheses, with normal mechanical function. The presence and severity of hemolysis was assessed on the basis of serum lactic dehydrogenase, serum haptoglobin, blood hemoglobin and reticulocyte levels as well as the presence of schistocytes. Overall, patients with SJM prostheses had greater frequency (51.2 vs 18.7%, p < 0.005) and severity (p < 0.005) of hemolysis than patients with MH prostheses, irrespective of position and size. No patient had decompensated anemia. The frequency of hemolysis was similar in both groups with double-valve replacement, whereas severity was greater with SJM than MH prostheses (p < 0.001). The number and position of the prostheses were correlated with severity of hemolysis: Double-valve replacement and mitral position were correlated with greater hemolysis than single-valve replacement (p < 0.01) and aortic position (p < 0.01). Valve size, cardiac rhythm and time from operation did not correlate either with frequency or severity of hemolysis. It is concluded that in normally functioning SJM and MH prostheses: (1) hemolysis is frequent but never severe; (2) SJM demonstrates greater frequency and severity when compared with MH valve; and (3) number, position, but not size, significantly affect the severity of hemolysis.

Simultaneous mechanical clot fragmentation and pharmacologic thrombolysis in acute massive pulmonary embolism

that technetium pyrophosphate scintigraphy has a very low sensitivity for cardiac amyloidosis. Our results suggest that none of the noninvasive parameters evaluated in this study for diagnosis of cardiac amyloidosis are highly sensitive. Thus, low voltage had a sensitivity of 80%, myocardial sparkling 45%, and technetium-99m-pyrophosphate uptake 23%. This low sensitivity, coupled with the previously mentioned low specificity, makes these findings unattractive for diagnosis of amyloidosis. An alternative approach to noninvasive diagnosis of cardiac amyloidosis was suggested by Carrol et al’ who noted that patients with cardiac amyloidosis tend to have low electrocardiographic voltages and high echocardiographic estimates of left ventricular mass. When the voltage/mass relation for cardiac amyloid patients is compared with that for patients with aortic valve (high voltage, high mass) or pericardial (low voltage, low mass) disease, clear differences emerge. Plotting voltage/mass relations for the patients in this study on a diagram developed by Carrol et al (Figure 1) would place 12 patients (80%) in a cardiac amyloid range (voltage 10 cm2/m2). This result makes the voltage/mass relation an attractive approach for diagnosis of cardiac amyloidosis. However, there are no reliable estimates of specificity for this technique. In conclusion, the present study examined several frequently used findings obtained by noninvasive techniques with regard to their sensitivity for diagnosis of cardiac amyloidosis. Our results suggest that the sensitivity ‘of both myocardial technetium uptake and echocardiographic observation of sparkling are low. However, voltage/mass relation diagrams appear to be a very promising technique for noninvasive diagnosis of these patients. The use and specificity of this technique need further study.

Effects of long-acting nifedipine on casual office blood pressure measurements, 24-hour ambulatory blood pressure profiles, exercise parameters and left ventricular mass and function in black patients with mild to moderate systemic hypertension

Thirty-nine black patients with mild to moderate hypertension were treated for 1 year with various long-acting preparations of nifedipine, during which time serial changes in 24-hour ambulatory blood pressure (BP), exercise performance, left ventricular (LV) mass index and LV systolic function were evaluated. Mean 24-hour ambulatory BP decreased from 156 +/- 15/99 +/- 8 to 125 +/- 10/79 +/- 6 mm Hg at 1 year (p less than 0.0001). LV mass index decreased from 130 +/- 40 to 114 +/- 39 g/m2 at 6 weeks (p less than 0.005) and to 95 +/- 32 at 1 year (p less than 0.0001). There was a significant reduction in septal and posterior wall thickness from 11.0 +/- 2.0 to 9.3 +/- 2.0 mm (p less than 0.0001) and from 10.9 +/- 2.0 to 9.3 +/- 2.0 mm (p less than 0.005), respectively. Cardiac index and fractional shortening changed insignificantly from 2.9 +/- 0.7 to 2.9 +/- 0.6 liters/min/m2, and from 35 +/- 5 to 36 +/- 6%, respectively. At 1 year, using a modified Bruce protocol, exercise time increased from 691 +/- 138 to 845 +/- 183 seconds (p less than 0.05); peak exercise and 1 minute post-effort systolic BP decreased from 240 +/- 26 to 200 +/- 21 mm Hg and from 221 +/- 27 to 169 +/- 32 mm Hg (p less than 0.05), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Excessive vasoconstriction in rheumatic mitral stenosis with modestly reduced ejection fraction

OBJECTIVESnThe primary hypothesis examined was that underfilling due to inflow obstruction accounts for modestly depressed ejection performance in mitral stenosis. Having found little evidence to support this hypothesis, we sought to determine other factors that might differentiate patients with different levels of ejection performance.nnnMETHODSnVentricular load and performance were compared in two groups of patients before and immediately after successful balloon valvuloplasty that was not complicated by mitral regurgitation: those in whom prevalvuloplasty ejection fraction was > or = 0.55 (group I, n = 10) and those in whom it was < 0.55 (group II, n = 11).nnnRESULTSnBefore valvuloplasty, mitral valve area was less in group II (0.65 cm2) than in group I (0.84 cm2, p = 0.02), but end-diastolic pressure (12 vs. 12 mm Hg in group I), end-diastolic wall stress (46 vs. 44 kdynes/cm2 in group I) and end-diastolic volume (152 vs. 150 ml in group I) were not less in group II, nor were these variables significantly reduced compared with those of a normal control group. In group II, end-systolic volume was larger (77 vs. 55 ml in group I, p = 0.001) and cardiac output was less (3.1 vs. 3.6 liters/min in group I, p = 0.03), possibly owing to higher systemic vascular resistance (2,438 vs. 1,921 dynes.s.cm-5 in group I, p = 0.05) and end-systolic wall stress (273 vs. 226 kdynes/cm2 in group I, p = 0.06), although mean arterial pressure in the two groups was similar (91 vs. 84 mm Hg in group I, p = 0.22). Group II patients also had higher values for pulmonary vascular resistance (712 vs. 269 dynes.s.cm-5 in group I, p = 0.03) and mean pulmonary artery pressure (47 vs. 29 mm Hg in group I, p = 0.02) despite similar values for mean left atrial pressure (20 vs. 18 mm Hg in group I, p = 0.35). After valvuloplasty, mitral valve area increased by 2.5- and 3-fold, respectively, in group I (to 2.1 cm2) and group II (to 2.0 cm2). Modest increases in left ventricular end-diastolic pressure, end-diastolic stress and end-diastolic volume (+9%) after valvuloplasty were statistically significant only for group II. End-systolic wall stress did not decline in either group II (281 kdynes/cm2) or group I (230 kdynes/cm2), and ejection fraction failed to increase significantly (0.49 to 0.51 for group II and 0.62 to 0.61 for group I) after valvuloplasty. Contractile performance estimated with a preload-corrected ejection fraction-afterload relation was within or near normal limits in all 19 patients in whom it was assessed.nnnCONCLUSIONSnExcessive vasoconstriction may account for the higher afterload, lower ejection performance and lower cardiac output observed in a subset of patients with mitral stenosis because contractile dysfunction could not be detected and left ventricular filling--which was not subnormal despite severe inflow obstruction--improved only modestly after valvuloplasty.

Frequency of prosthetic valve-related complications with very low level warfarin anticoagulation combined with dipyridamole after valve replacement using St. Jude Medical prostheses

The safety of a very low level of anticoagulation combined with dipyridamole in a rheumatic population (mean age 31 +/- 13 years) with the St. Jude Medical (SJM) prosthesis has not yet been tested. Furthermore, no data are available on the safety of relatively infrequent monitoring of anticoagulation levels and of the necessity for different therapeutic targets according to valve position, number of risk factors, and other baseline risk factors for thromboembolism. In this study, the performance of the SJM prosthesis was tested using a target international normalized ratio (INR) of 2.0 to 2.5 combined with dipyridamole 300 mg/day applied uniformly to all patients. Clinical, biochemical, and echocardiographic data were acquired prospectively in 200 consecutive patients at 3-month intervals. Follow-up (mean 27 +/- 13 months) was complete in 95% of patients. Thirteen patients died (2.9%/patient year). Severe left ventricular dysfunction was the cause of death in 10 of 13 patients. Probability of survival (Kaplan-Meier) was 0.92 at 36 months and of event-free survival 0.84 at 36 months. The median INR was 2.0 +/- 0.9. Valve obstruction did not occur, and there were 3 thromboembolic events (0.6%/patient year). Incidence of bleeding was 1.6%/patient year (n = 7) and was major (hemorrhagic stroke) in 1 (0.2%/patient year). Thus, the SJM prosthesis performs very well despite the use of very low level warfarin anticoagulation combined with dipyridamole. A 3-month assessment of the anticoagulation level is safe. Left ventricular dysfunction rather than valve-related complications is the leading cause of mortality in this population.

Results of percutaneous balloon mitral valvotomy in young adults

The results of percutaneous balloon mitral valvotomy (PBMV) were evaluated in 235 young patients (mean age 29 +/- 11 years) with symptomatic rheumatic mitral stenosis, and the single-balloon Inoue technique was compared with the double-balloon Mansfield technique. PBMV was associated with a significant increase in Gorlin mitral valve area (0.78 +/- 0.23 to 1.61 +/- 0.64 cm2; p < 0.001), and improvement in New York Heart Association functional class (2.78 +/- 0.59 to 1.28 +/- 0.58; p < 0.001). Mitral regurgitation increased significantly (0.4 +/- 0.6 to 1.3 +/- 1.0; p < 0.001), but was significant (> or = 3+) only in 19 patients (8%). Comparison of the Inoue and Mansfield techniques showed a significantly lower Gorlin mitral valve area after PBMV (1.55 +/- 0.56 vs 1.74 +/- 0.74 cm2; p < 0.05), but a lower incidence of mitral regurgitation by color Doppler echocardiography (1.1 +/- 0.7 vs 1.5 +/- 0.8; p < 0.05) in the Inoue group. Patients were divided into those with nonpliable (valve score > 8; group I) and pliable (score < or = 8; group II) valves. Although significant increases in mitral valve area were obtained in both groups, mitral valve area by planimetry was significantly lower in group I (1.49 +/- 0.46 vs 1.86 +/- 0.44 cm2; p < 0.05), whereas there was no difference in the amount of color Doppler mitral regurgitation (1.5 +/- 1.0 vs 1.2 +/- 0.7; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of severe pulmonary hypertension on outcome of balloon mitral valvotomy

Abstract Severe pulmonary hypertension is no longer considered a major risk factor for patients undergoing surgical treatment of mitral stenosis. 1 Whereas balloon mitral valvotomy (BMV) has recently gained favor as an alternative to the surgical treatment of patients with uncomplicated, pliable mitral stenosis, 2 the safety and efficacy of BMV in patients with severe pulmonary hypertension has, to our knowledge, been addressed in only 1 study. From the experience at Beth Israel Hospital, Levine et al 3 reported excellent immediate results and a low incidence of complications of BMV in 14 patients with moderate to severe pulmonary hypertension. Nevertheless, during our early BMV experience, we approached this subset of patients with trepidation for several reasons: (1) because of their more precarious hemodynamic status, they may be less tolerant of the stress of the procedure; (2) the transseptal puncture may be more difficult because of large right-sided chambers; and (3) because of tighter mitral stenosis, the valve may be more difficult to cross or more susceptible to tearing. This paper reports our BMV results in 52 such patients with severe pulmonary hypertension (mean pulmonary artery pressure ≥50 mm Hg).

Transesophageal echocardiography in congenital submitral aneurysm.

teries.12 A third reason may be that postglomerular vasoconstriction occurs through an autoregulatory mechanism unrelated to angiotensin It. This, together with the former possibility, was not ruled out in the present study, but if relevant, adds further evidence that the role of the renin-angiotensin system in coarctation is a minor one. In conclusion, acute administration of captopril to patients before and after surgical correction showed variations in renal function, as observed in normal subjects. The results thus indicate that angiotensin II-mediated renal autoregulation is not essential for the maintenance of a normal filtration in patients with aortic coarctation. Results from experimental coarctation further suggest this conclusion to be valid also when renal angiotensin II formation is blocked over a prolonged period of time.13