Pinhas Sareli

Obstruction of mechanical heart valve prostheses: Clinical aspects and surgical management

One hundred patients (32 male) aged 5 months to 82 years (median 32 years) underwent 106 surgical procedures for 112 mechanical prosthetic valves obstructed by a thrombus (n = 61) or pannus (n = 7), or both (n = 44), between January 1, 1980 and December 31, 1989. The position of the obstructed prosthesis was aortic in 51 patients (48%), mitral in 49 (46%) and both aortic and mitral in 6 (6%). The types of obstructed prosthetic valves were Björk-Shiley (n = 51), St. Jude (n = 41) and Medtronic-Hall (n = 20). The time interval between valve replacement and obstruction ranged from 6 weeks to 13 years (median 4 years). Of 63% of patients in whom coagulation variables were available at the time of obstruction, 70% were receiving inadequate anticoagulant therapy. In 63% of the procedures the patient was in New York Heart Association functional class IV. Two patients underwent preoperative thrombolysis with incomplete results. Operative procedures included valve replacement (n = 81), valve declotting and excision of pannus (n = 23) and aortic valve replacement and mitral valve declotting (n = 2). The early mortality rate was 12.3% (13 patients), and there was no difference between surgery for mitral prostheses (12.2%) versus aortic prostheses (13.7%). The perioperative mortality rate was 17.5% (11 of 63 patients) in patients in functional class IV and 4.7% (2 of 43 patients) in those in functional classes I to III (p less than 0.05). For valve replacement, the mortality rate was 12% (10 of 81 patients) and for declotting of the prosthesis 13% (3 of 23 patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Peripartum cardiomyopathy: analysis of clinical outcome, left ventricular function, plasma levels of cytokines and Fas/APO-1

OBJECTIVES 1) To evaluate the outcome of patients with peripartum cardiomyopathy (PPC) on current treatment for heart failure, 2) to assess the circulating plasma levels of cytokines and Fas receptors and 3) to identify predictors of prognosis. BACKGROUND Previous studies in patients with PPC were done when angiotensin-converting enzyme (ACE) inhibitors and beta-adrenergic blocking agents were not routinely used in heart failure. Inflammatory cytokines play an important role in the pathogenesis and progression of heart failure of other etiologies. However, there is a paucity of data regarding cytokine expression in patients with PPC. Plasma concentrations of Fas receptors (an apoptosis-signalling receptor) have not been reported in this population. METHODS We followed prospectively 29 consecutive black women with PPC. All patients were treated with diuretics, digoxin, enalapril and carvedilol. Echocardiograms were performed at baseline and after six months of treatment. Cytokine and soluble Fas/APO-1 plasma levels were measured at baseline. RESULTS Tumor necrosis factor-alpha, interleukin-6 and Fas/APO-1 levels were significantly elevated in the study patients compared with 20 healthy volunteers. Eight patients died. sFas/APO-1 levels were significantly higher in patients who died compared with survivors (8.98 +/- 4.5 vs. 5.33 +/- 3 U/ml, respectively, p = 0.02). At six months, ejection fraction improved from 26.7 +/- 10 to 42.7 +/- 16%, p = 0.00003, with an increment of more than 10 U in 10 patients (28.1 +/- 4 to 51.9 +/- 8%, p = 0.000008). CONCLUSIONS Cytokine and sFas levels are elevated in patients with PPC. Despite treatment with ACE inhibitors and beta-blockers, mortality remains high. However, in 34% of the patients, left ventricular function almost completely normalized.

Randomised investigation of effects of pentoxifylline on left-ventricular performance in idiopathic dilated cardiomyopathy

BACKGROUND There is accumulating evidence that inflammatory cytokines have an important role in the pathogenesis of heart failure. Plasma concentrations of tumour necrosis factor alpha (TNF-alpha) are high in heart failure and have been correlated with the severity of symptoms. Pentoxifylline suppresses the production of TNF-alpha. This study aimed to assess the effects of pentoxifylline on left-ventricular function and functional class in patients with idiopathic dilated cardiomyopathy. METHODS We undertook a single-centre, prospective, double-blind, randomised, placebo-controlled trial, in which 28 patients with idiopathic dilated cardiomyopathy were assigned pentoxifylline 400 mg three times daily or matching placebo. Clinical, echocardiographic, and radionuclide assessments were done at baseline and after 6 months of treatment. Primary endpoints were New York Heart Association (NYHA) functional class and left-ventricular function. FINDINGS Baseline characteristics were similar in the two groups. Four patients died during the study period, all in the placebo group. After 6 months of treatment, the proportion of patients in NYHA functional class I or II was higher in the pentoxifylline group than in the placebo group (14/14 vs 10/14; p=0.01), and ejection fraction was higher in the pentoxifylline group than in the placebo group (mean 38.7% [SD 15.0] vs 26.8% [11.0], p=0.04). At 6 months, TNF-alpha plasma concentrations were significantly lower in the pentoxifylline-treated group than in the placebo group (2.1 [1.0] vs 6.5 [5.0] pg/mL, p=0.001). INTERPRETATION Our results suggest that pentoxifylline improves symptoms and left-ventricular systolic function in patients with idiopathic dilated cardiomyopathy. These results must be confirmed in larger-scale trials.

The early recognition of right ventricular infarction: diagnostic accuracy of the electrocardiographic V4R lead.

The sensitivity and specificity of ST-segment elevation in the right precordial lead V4R as an early indicator of right ventricular infarction were examined in a consecutive series of 110 patients admitted for acute inferior myocardial infarction. The sensitivity was 82.7%, the specificity 76.9% and the positive predictive value 70% in 58 patients with right ventricular infarction documented by autopsy or a combination of radionuclide ventriculography and one or more of the following tests: echocardiography, technetium- 99m pyrophosphate scintigraphy and hemodynamic monitoring. The negative predictive value was 87.7%. Because of its simplicity and its high sensitivity and specificity, recording of V4R should be an intrinsic part of the early evaluation and electrocardiographic examination of acute inferior wall infarction.

Prediction of outcome after valve replacement for rheumatic mitral regurgitation in the era of chordal preservation.

BACKGROUND Noninvasive predictors of important outcomes after valve replacement for mitral regurgitation have not been examined in a rheumatic population (in whom the results of valve repair are suboptimal) in the era of chordal preservation. Timing of valve replacement thus remains a difficult question in rheumatic mitral regurgitation. METHODS AND RESULTS Of 278 patients followed after valve replacement, 66 had pure or predominant mitral regurgitation, and in 61 of these the etiology was rheumatic. The mean age was 24 years. After a mean follow-up of 24 +/- 10 months, the ability of preoperative clinical and echocardiographic data to predict outcome was assessed prospectively, and the possible impact of chordal preservation (n = 35) on survival and post-operative left ventricular function was examined retrospectively. There were no perioperative deaths. There were six postoperative deaths, all the result of heart failure and all related to left ventricular dysfunction. The mean probability of survival was .90 at 16 months. In a stepwise Cox proportional hazards regression analysis, the only independent predictor of postoperative death was preoperative end-systolic diameter. According to a logistic model, the probabilities of death (n = 6) and death or severe heart failure (n = 7) increased abruptly at a preoperative end-systolic diameter of 51 mm (probabilities, .23 and .31, respectively), and the accuracy of this cut point for predicting outcomes was 97% and 98%, respectively. Multiple linear regression analysis identified a large preoperative end-systolic diameter and the need to use tricuspid annuloplasty as significant independent predictors of postoperative fractional shortening; the use of chordal preservation (n = 35) was not a predictor of postoperative fractional shortening. A good outcome was predicted at a preoperative end-systolic diameter of 40 mm: probability of death or heart failure was .0001, and predicted mean postoperative fractional shortening was 0.27 after mitral valve replacement without tricuspid annuloplasty. CONCLUSIONS When preoperative end-systolic diameter is more than 50 mm, a poor postoperative outcome is predicted despite chordal preservation in relatively young patients with rheumatic mitral regurgitation, and alternative strategies should therefore be considered. When preoperative end-systolic diameter is 40 mm or less, an excellent outcome is predicted, and close observation without surgery would appear to be reasonable in the absence of symptoms.

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

OBJECTIVES This study examined the long-term (3-month) effects of nebivolol, a new beta-adrenergic blocking agent, on cardiac performance in patients with dilated cardiomyopathy. BACKGROUND Several 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. METHODS Twenty-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). RESULTS Heart 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. CONCLUSIONS Nebivolol 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.

The spectrum of severe rheumatic mitral valve disease in a developing country. Correlations among clinical presentation, surgical pathologic findings, and hemodynamic sequelae.

Bland and Jones [1], in their benchmark report on rheumatic fever and rheumatic heart disease in 1951, documented a mortality rate of 50% by age 20 years among young patients presenting with rheumatic mitral valve disease before 1920. With the advent of antibiotics, the incidence and severity of rheumatic fever and acute rheumatic carditis have declined markedly in the Western world [2, 3]. In the United States, the decline in rheumatic disease resulting from antimicrobial therapy was so dramatic that several important issues relating to the natural history of this condition have never been resolved. Specifically, the high early mortality rate among young patients with acute rheumatic carditis [1, 4] has not been explained. In this context, Bland and Jones [1] did report a high prevalence of mild mitral regurgitation early in the course of the disease but felt that this lesion was benign. The prevalence and natural history of pure, severe rheumatic mitral regurgitation have not been established, and its unique surgical anatomy has not been well characterized. In developing areas, where predisposing factors to rheumatic fever persist and prophylactic penicillin therapy is often inadequate, acute rheumatic carditis still frequently follows a fulminant course, resulting in death or severe disability at an early age [5-8]. In South Africa, the sociopolitical situation is such that abject poverty and deprivation are often juxtaposed with sophisticated tertiary care services. The availability of the latter, specifically cardiac surgery, for patients with this disease permitted us to analyze clinical, hemodynamic, and surgical pathologic data that had not been previously correlated. Methods We retrospectively studied 748 consecutive patients with rheumatic heart disease who had mitral valve surgery between 1983 and 1986 at Baragwanath Hospital in South Africa. All patients were blacks living either in townships in the environs of the hospital (equivalent to inner-city areas in the metropolitan United States) or in rural areas. Eleven patients in whom concurrent infective endocarditis or primary degenerative leaflet disease (1 patient) confounded evaluation of the hemodynamic severity of the rheumatic lesion itself were excluded from the analysis. Of the remainder, 520 were female and 217, male. Patients ranged in age from 4 to 73 years (mean, 27 13 years [SD]; median, 25 years); 271 (37%) were 20 years of age or younger. All were in New York Heart Association (NYHA) class 3 or 4 and receiving maximal medical treatment. Preoperative Classification of Valve Lesions Before surgery, all patients were examined independently by at least two cardiologists. Mitral valve lesions were classified as purely regurgitant, purely stenotic, or mixed according to recognized clinical, radiologic, and echocardiographic criteria [9]. Mitral regurgitation was considered to be pure when associated with unrestricted valve leaflet excursion and a normal mitral orifice area as assessed by two-dimensional echocardiography. Pure mitral stenosis was diagnosed when no clinical or echocardiographic evidence for regurgitation was found. Mixed mitral valve disease was diagnosed when features of both regurgitation and stenosis were present. Cases in which discordance existed among clinical, hemodynamic, and surgical pathologic assessments were excluded from the analysis. Surgical Evaluation Hemodynamic Assessment The hemodynamic severity of valve lesions was confirmed by measurements of left atrial, left ventricular, and right ventricular pressures using fluid-filled catheters connected through strain gauge transducers (Statham, Oxnard, California) to a multichannel recorder (Honeywell Meddars, Lenexa, Kansas). The transmitral end-diastolic gradient (timed according to the R wave on the electrocardiogram) was determined by analysis of simultaneous left atrial and left ventricular pressure recordings. The ratio of left atrial V wave to mean left atrial pressure was calculated as an index of the hemodynamic severity of mitral regurgitation [10]. In 74 patients (10%), pressure measurements were not obtained for technical reasons or because of hemodynamic instability. Surgical Anatomy After cardiotomy, mitral valves were examined independently by two experienced surgeons according to a standard protocol, implemented in all patients having rheumatic valve surgery at Baragwanath Hospital between 1983 and 1986 at the instigation of one of the surgeons who was then doing research in this area. Valve leaflets were assessed for their pliability as well as for evidence of retraction (scarring) or calcification. Valve commissures were evaluated for evidence of fusion. Mitral valve prolapse was diagnosed at operation if the free edge of one or more scallops of a leaflet, almost invariably the anterior, could be retracted toward the left atrium beyond the free margin of the complementary leaflet and above the plane of the mitral annulus without applying tension to the chordae tendineae [5, 11]. The size of the mitral annulus and the length of the chordae tendineae were assessed. The size of the mitral annulus was graded by inspection using a 4-point scale from 0 (normal size) to 3+ (markedly dilated). In addition, the annular diameter was measured using valve sizers in all patients who had insertion of mechanical prostheses or valve rings (Carpentier, Santa Ana, California). The chordae tendineae were assessed for length (elongated, shortened, or normal), fusion, and evidence of rupture. Among patients who had mitral valvuloplasty, the requirement for chordal shortening procedures was used as ancillary evidence for the presence of chordal elongation. Surgical Classification of Valve Lesions The hemodynamic and anatomic features that were considered diagnostic of pure mitral regurgitation included absent or minimal end-diastolic gradient across the mitral valve; pliable, freely mobile mitral valve leaflets; and absence of commissural fusion or subvalvular disease. Pure mitral stenosis was confirmed at surgery in patients with no clinical or echocardiographic evidence for mitral regurgitation when there was marked commissural fusion and a substantial transmitral end-diastolic gradient. Assessment of Rheumatic Activity Clinical Evaluation Rheumatic activity was diagnosed preoperatively when there was serologic evidence for antecedent group A -hemolytic streptococcal infection in addition to at least two major (or one major plus two minor) criteria of acute rheumatic fever (revised Jones criteria) [12]. Macroscopic Evaluation Valves were examined during surgery for the macroscopic features of active rheumatic carditis that have been described [5, 13]: fibrinous pericarditis with epicardial involvement; pinhead vegetations on the free edges of the valve leaflets in the absence of infective endocarditis; and nonspecific signs of acute inflammation including edema, erythema, and hemorrhage within leaflet tissue. Histologic Evaluation Where sufficient cardiac tissue was available for adequate histologic assessment, the following light microscopic findings were used as criteria of rheumatic activity [13, 14]: fibrinoid necrosis in valve leaflet or annular tissue; polymorphonuclear or histiocyte infiltration; edema; and neovascularization. Analysis of Data For continuous variables, such as pressure data, analysis of variance with the Tukey allowance for multiple comparisons was used to compare three or more groups, and two-sample t-tests were used in instances when only two groups were compared. For categorical data, such as the prevalence of mitral valve prolapse, chi-square tests were used. Three x two contingency tables were constructed to establish the presence of intergroup differences; individual groups were then compared using the Bonferroni correction for multiple comparisons. Statistical differences were recorded using two-tailed P values. Results Correlation between Preoperative and Surgical Classification of Valve Lesions Surgical and preoperative classifications of valve lesions were in agreement in 714 of 737 (97%) cases. The 23 patients in whom discordance existed between the preoperative and surgical assessment of the mitral valve lesion were excluded from the analysis. Relative Prevalence of Valve Lesions When the entire patient population was considered, the three types of mitral valve lesion were documented with similar frequency: Two hundred nineteen patients had pure mitral regurgitation (31%), 275 had pure stenosis (38%), and 220 had mixed lesions (31%). However, 36 of 46 patients (78%) who had surgery in the first 10 years of life had pure mitral regurgitation; pure regurgitation was the most common lesion in patients 20 years of age and younger, accounting for 58% of surgically treated rheumatic mitral valve disease (158 of 271 cases) in this age group. Eighty-nine percent (194 of 219) of patients with pure mitral regurgitation were 30 years of age or younger (Figure 1). In contrast, the prevalence of mitral stenosis increased with age. Only 20% of patients with pure stenosis (55 of 275) were less than 20 years of age. Mixed mitral valve disease also increased in frequency until the fourth decade, after which its prevalence declined slightly. Figure 1. Time-course analysis (by decades) of the relative prevalence of pure mitral regurgitation, mixed mitral valve disease, and pure mitral stenosis. Hemodynamic Data Average values for mean left atrial pressure were similarly increased in all three groups (24 mm Hg for pure regurgitation and pure stenosis and 25 mm Hg for mixed disease). Pure mitral regurgitation was also characterized by a markedly raised left atrial V wave (46 18 mm Hg) and an average V wave:mean left atrial pressure ratio of 1.9:1, indicating severe hemodynamic compromise [10]. In addition, left ventricular end-diastolic pressure was elevated, whereas the end-diastolic gradient across the mitral valve was trivial. Pure mitral stenosis

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)

Beneficial Effects of Pentoxifylline in Patients With Idiopathic Dilated Cardiomyopathy Treated With Angiotensin-Converting Enzyme Inhibitors and Carvedilol Results of a Randomized Study

Background —We previously reported beneficial effects of pentoxifylline, a xanthine-derived agent known to inhibit the production of tumor necrosis factor-&agr;, in patients with idiopathic dilated cardiomyopathy treated with diuretics, digoxin, and ACE inhibitors. Since then, 3 large clinical trials showed important clinical benefits of &bgr;-blockers in this population. Therefore, we designed the present study to establish whether in patients with heart failure already receiving treatment with ACE inhibitors and &bgr;-blockers, the addition of pentoxifylline would have an additive beneficial effect. Methods and Results —In a single-center, prospective, double-blind, randomized, placebo-controlled study, 39 patients with idiopathic dilated cardiomyopathy were randomized to pentoxifylline 400 mg TID (n=20) or placebo (n=19) if they had a left ventricular ejection fraction <40% after 3 months of therapy with digoxin, ACE inhibitors, and carvedilol. Primary end points were New York Heart Association functional class, exercise tolerance, and left ventricular function. Patients were followed up for 6 months. Five patients died (3 in the placebo group). Patients treated with pentoxifylline had a significant improvement in functional class compared with the placebo group (P =0.01), with an increment in exercise time from 9.5±5 to 12.3±6 minutes (P =0.1). Left ventricular ejection fraction improved from 24±9% to 31±13%, P =0.03, in the treatment group. Conclusions —In patients with idiopathic dilated cardiomyopathy, the addition of pentoxifylline to treatment with digoxin, ACE inhibitors, and carvedilol is associated with a significant improvement in symptoms and left ventricular function.

The addition of pentoxifylline to conventional therapy improves outcome in patients with peripartum cardiomyopathy.

We have reported previously that despite treatment with angiotensin‐converting enzyme inhibitors and β blockers, the outcome of patients with peripartum cardiomyopathy (PPC) remains unfavorable. Similar to other etiologies of left ventricular dysfunction, we found elevated levels of tumor necrosis factor‐α (TNF‐α) in this group of patients. In the present study we sought to evaluate the effects of pentoxifylline, a drug known to inhibit the production of TNF‐α, on clinical status, left ventricular function, and circulating plasma levels of TNF‐α, in patients with PPC. We followed prospectively 59 consecutive women with PPC. The first 29 patients (group 1) were treated with diuretics, digoxin, enalapril and carvedilol. The next 30 consecutive patients (group 2) received pentoxifylline 400 mg TID in addition to the previous therapy. Clinical evaluation, echocardiograms and TNF‐α determinations were performed at baseline and after 6 months of treatment. Patients in the pentoxifylline group were older and had a higher E/A ratio. Nine patients died (eight in group 1, P‐0.009 between groups). A combined end‐point of poor outcome defined as either death, failure to improve the left ventricular ejection fraction >10 absolute points or functional class III or IV at latest follow‐up, occurred in 52% of patients in group 1 and 27% of patients in group 2 (P‐0.03). Treatment with pentoxifylline (P‐0.04) was the only independent predictor of outcome. In conclusion, the results of this study suggest that the addition of pentoxifylline to conventional treatment, improves outcome in patients with peripartum cardiomyopathy.