Lieng H. Ling

Clinical Outcome of Mitral Regurgitation Due to Flail Leaflet

BACKGROUND Mitral regurgitation due to flail leaflet is difficult to manage, because it is frequently asymptomatic yet carries a high risk of left ventricular dysfunction and because the natural history of the condition is poorly defined. METHODS We obtained clinical follow-up data through 1994-1995 in 229 patients with isolated mitral regurgitation due to flail leaflet; this condition was first diagnosed by echocardiography between 1980 and 1989. RESULTS The 86 patients who were treated medically had a mortality rate significantly higher than expected (6.3 percent yearly, P=0.016 for the comparison with the expected rate in the U.S. population according to the 1990 census). Independent determinants of mortality were an older age, the presence of symptoms, and a lower ejection fraction. Patients who were even transiently in New York Heart Association functional class III or IV had a high mortality rate (34 percent yearly), but the rate was also notable (4.1 percent yearly) among those in class I or II. At 10 years, the mean (+/- SE) rates of heart failure, atrial fibrillation, and death or surgery were 63 +/- 8, 30 +/- 12, and 90 +/- 3 percent, respectively. In a multivariate analysis, surgical correction of mitral regurgitation (performed in 143 patients) was associated with a reduced mortality rate (hazard ratio, 0.29; 95 percent confidence interval, 0.15 to 0.56; P<0.001). CONCLUSIONS When treated medically, mitral regurgitation due to flail leaflet is associated with excess mortality and high morbidity. Surgery is almost unavoidable within 10 years after the diagnosis and appears to be associated with an improved prognosis; this finding suggests that surgery should be considered early in the course of the disease.

Constrictive Pericarditis in the Modern Era Evolving Clinical Spectrum and Impact on Outcome After Pericardiectomy

BACKGROUND The clinical spectrum of constrictive pericarditis (CP) has been affected by a change in incidence of etiological factors. We sought to determine the impact of these changes on the outcome of pericardiectomy. METHODS AND RESULTS The contemporary spectrum of CP in 135 patients (76% male) evaluated at the Mayo Clinic from 1985 to 1995 was compared with that of a historic cohort. Notable trends were an increasing frequency of CP due to cardiac surgery and mediastinal radiation and presentation in older patients (median age, 61 versus 45 years). Perioperative mortality decreased (6% versus 14%, P = 0.011), but late survival was inferior to that of an age- and sex-matched US population (57+/-8% at 10 years). The long-term outcome was predicted independently by 3 variables in stepwise logistic regression analyses: (1) age, (2) NYHA class, and most powerfully, (3) a postradiation cause. Of 90 late survivors in whom functional class could be determined, functional status had improved markedly (2.6+/-0.7 at baseline versus 1.5+/-0.8 at latest follow-up [P<0.0001]), with 83% being free of clinical symptoms. CONCLUSIONS The evolving profile of CP, with increasingly older patients and those with radiation-induced disease in the past decade, significantly affects postoperative prognosis. Long-term results of pericardiectomy are disappointing for some patient groups, especially those with radiation-induced CP. By contrast, surgery alleviates or improves symptoms in the majority of late survivors.

Atrial fibrillation complicating the course of degenerative mitral regurgitation: Determinants and long-term outcome

OBJECTIVES The study was done to define the incidence, determinants and prognostic implications of onset of atrial fibrillation (AF) during follow-up of mitral regurgitation (MR) initially in sinus rhythm. BACKGROUND The rates and clinical implications of AF in MR are undefined. METHODS We analyzed the occurrence of AF under conservative management in two populations of patients with degenerative MR in sinus rhythm at diagnosis: 1) 360 patients (65 +/- 13 years, 74% men) with MR due to flail leaflets; and 2) 89 residents of Olmsted County, Minnesota (67 +/- 17 years, 56% men) with grade 3 or 4 MR due to simple mitral valve prolapse (MVP) diagnosed echocardiographically. RESULTS In patients with MR due to flail leaflets, AF rates at 5 and 10 years were 18 +/- 3% and 48 +/- 6%, respectively, and the linearized rate was 5.0 +/- 0.7% per year. Development of AF during follow-up was independently associated with high risk of cardiac death or heart failure (adjusted risk ratio 2.23, p = 0.025). The AF rate at 10 years was higher in patients >or=65 years (75 +/- 10% vs. 24 +/- 6%, p < 0.0001) and in those with baseline left atrial (LA) dimension >or=50 mm (67 +/- 8% vs. 37 +/- 9%, p < 0.001). In multivariate analysis, independent baseline predictors of AF were age and LA diameter (both p < 0.01). In patients with MR due to MVP, similar rates of AF (41 +/- 7% vs. 44 +/- 6% at nine years, p > 0.50) and predictors of AF (age and LA dimension, both p < 0.006) were noted. CONCLUSIONS In patients with degenerative MR in sinus rhythm at diagnosis, the incidence of AF occurring under conservative management is high and similar whether the cause of MR is flail leaflet or simple MVP. After onset of AF, an increased cardiac mortality and morbidity are both observed under conservative management. The risk of AF increases with advancing age and larger LA dimension. These data suggest that the clinical management of MR should take into account the high incidence, excess risk, and predictors of AF.

Early Surgery in Patients With Mitral Regurgitation Due to Flail Leaflets A Long-term Outcome Study

BACKGROUND The optimal timing for surgery in patients with mitral regurgitation is disputed. Because of the frequency of left ventricular dysfunction, which is difficult to predict, early surgery has been recommended, but its potential benefits have not been demonstrated. METHODS AND RESULTS The outcomes of 221 patients (mean age, 65 +/- 13 years; 71% males) with flail leaflets diagnosed with two-dimensional echocardiography between 1980 and 1989 who were eligible for operation were analyzed. Group I comprised 63 patients who had early mitral valve surgery (within 1 month after diagnosis). Group II comprised 158 patients initially treated conservatively (80 of whom were operated on later). Group I patients were younger (P=.009), had more symptoms (P<.0001), and were more frequently in atrial fibrillation (P=.023) than group II patients. There was no difference in ejection fraction between the groups. The early surgery strategy was followed by an improved overall survival rate (P=.028) and a lower incidence of cardiovascular deaths (P=.025), congestive heart failure (P=.046), and new chronic atrial fibrillation (P=.032), as confirmed by multivariate analysis (adjusted risk ratios of 0.31, 0.18, 0.38, and 0.05, respectively; all P<.02). CONCLUSIONS In patients with mitral regurgitation due to flail leaflets, the strategy of early surgery versus conservative management is associated with an improved long-term survival rate, decreased cardiac mortality, and decreased morbidity after diagnosis. This outcome advantage suggests that early surgery is a reasonable treatment option to be considered in low-risk candidates with repairable valves and severe mitral regurgitation.

Sudden Death in Mitral Regurgitation Due to Flail Leaflet

OBJECTIVES We sought to assess the incidence and determinants of sudden death (SUD) in mitral regurgitation due to flail leaflet (MR-FL). BACKGROUND Sudden death is a catastrophic complication of MR-FL. Its incidence and predictability are undefined. METHODS The occurrence of SUD was analyzed in 348 patients (age 67 +/- 12 years) with MR-FL diagnosed echocardiographically from 1980 through 1994. RESULTS During a mean follow-up of 48 +/- 41 months, 99 deaths occurred under medical treatment. Sudden death occurred in 25 patients, three of whom were resuscitated. The sudden death rates at five and 10 years were 8.6 +/- 2% and 18.8 +/- 4%, respectively, and the linearized rate was 1.8% per year. By multivariate analysis, the independent baseline predictors of SUD were New York Heart Association (NYHA) functional class (p = 0.006), ejection fraction (p = 0.0001) and atrial fibrillation (p = 0.059). The yearly linearized rate of sudden death was 1% in patients in functional class I, 3.1% in class II and 7.8% in classes III and IV. However, of 25 patients who had SUD, at baseline, 10 (40%) were in functional class I, 9 (36%) were in class II and only 6 (24%) in class III or IV. In five patients (20%), no evidence of risk factors developed until SUD. In patients with an ejection fraction > or =60% and sinus rhythm, the linearized rate of SUD was not different in functional classes I and II (0.8% per year). Surgical correction of MR (n = 186) was independently associated with a reduced incidence of SUD (adjusted hazard ratio [95% confidence interval] 0.29 [0.11 to 0.72], p = 0.007). CONCLUSIONS Sudden death is relatively common in patients with MR-FL who are conservatively managed. Patients with severe symptoms, atrial fibrillation and reduced systolic function are at higher risk, but notable rates of SUD have been observed without these risk factors. Correction of MR appears to be associated with a reduced incidence of SUD, warranting early consideration of surgical repair.

Atropine augmentation in dobutamine stress echocardiography : Role and incremental value in a clinical practice setting

OBJECTIVES This study sought to evaluate the role and incremental value of atropine in a large patient group undergoing dobutamine stress echocardiography. BACKGROUND The use of atropine to potentiate dobutamine stress is not standard practice. Although the utility of atropine has been described, data on its incremental value remain limited and do not exist for a routine clinical practice setting. METHODS Dobutamine stress echocardiography was performed in 1,171 patients with use of a standard protocol. Atropine (maximal dose 2.0 mg) was given to 299 patients (26%) who did not attain target heart rate. Coronary angiography was performed in 183 patients (46 received atropine), 148 of whom were found to have significant coronary artery disease (> or = 70% diameter stenosis in a major epicardial vessel, > or = 50% stenosis for left main coronary artery disease). All tests were reviewed independently by experienced observers. RESULTS There were no major adverse events. Patients receiving atropine had a lower rest heart rate (65 vs. 74 beats/min, p < 0.0001) and more often received beta-adrenergic blocking agents (49% vs. 14%, p < 0.0001). Of 444 patients in whom stress-induced ischemia developed, 70 (16%) required atropine before ischemia became evident. Sensitivity for detection of significant coronary artery disease was 90% with dobutamine alone and 95% after the addition of atropine. In 66 patients with normal wall motion at rest, test sensitivity was 65% before and 84% after atropine was given. Atropine use did not compromise test specificity. New diagnostic information was obtained in 20 (50%) of 40 patients with angiographic coronary artery disease given atropine. Proportionately more patients with single-vessel disease required atropine before an ischemic response was observed; this effect appeared related to the higher ischemic threshold in these patients. CONCLUSIONS Augmentation of heart rate had a modest influence on the overall diagnostic sensitivity of dobutamine stress echocardiography in our study cohort. However, it was particularly helpful in patients receiving beta-blockers and those with milder coronary disease. Despite the use of > or = 1 mg of atropine in some patients, this incremental value was not achieved at the expense of safety.

Calcific constrictive pericarditis: is it still with us?

The presence of pericardial calcification on radiography strongly suggests constrictive pericarditis in patients with symptoms of heart failure (1, 2). In a 1959 study, calcification was documented in up to 90% of all cases (3), usually after tuberculous pericarditis. However, because of the decrease in rates of tuberculosis and the increase in iatrogenic causes of constriction (4, 5), calcific constrictive pericarditis is believed to be extremely uncommon in the United States; it is now reported in as few as 5% of all cases of constrictive pericarditis (5). We reviewed our experience with pericardial constriction during the past decade and analyzed the clinical, diagnostic, and surgical profiles of patients with calcific constrictive pericarditis to determine the relevance of pericardial calcification in the current practice of cardiovascular medicine. Methods From January 1985 through June 1995, 135 patients at the Mayo Clinic, Rochester, Minnesota, had constrictive pericarditis confirmed surgically (n=133) or by autopsy (n=2). We excluded patients who had recurrent pericarditis or pericardial thickening but no other evidence of constriction. The study sample consisted of 103 men (76%) and 32 women (24%), all of whom were native U.S. citizens (mean age SD, 56 16 years [range, 11 to 78 years]). We divided patients into two groups: 36 patients with pericardial calcification on chest radiographs (group I) and 99 patients without (group II). All radiographs were reviewed by two experienced observers, including a cardiac radiologist. The clinical profile, diagnostic findings, and postoperative outcomes for both groups were compared to determine the associations of each of these variables with calcific disease. Echocardiography was performed with commercially available ultrasonography instruments. Atrial dimensions were determined by averaging three measurements made by a single observer who was blinded to clinical information; atrial volumes were derived by using the methods of Sanfilippo and colleagues (6). In most cases, computed tomography was performed with the C-100 electron-beam scanner (Imatron, Inc., San Francisco, California). Pericardiectomy was not performed in 1 of the 133 patients whose diagnosis was confirmed at surgery. Information on the vital status of the other 132 patients (36 in group I and 96 in group II) was obtained by review of the medical records; by mailed questionnaires; and by telephone calls to patients, relatives, or physicians. Follow-up was complete for 134 of 135 patients in August 1996. Definitions For uniformity with previous studies, perioperative death was defined as death that occurred within 30 days of surgery. However, we included all deaths that occurred during hospitalization for pericardiectomy when analyzing the predictors of this outcome. Late death was defined as death that occurred at least 30 days after pericardiectomy, unless it occurred during hospitalization for the procedure. Statistical Analysis Categorical variables were expressed as percentages and were compared by using the chi-square test. Continuous variables were expressed as the mean 1 SD and were compared by using the two-sample Wilcoxon rank-sum test. Rates of overall survival, perioperative death, and late death were estimated for groups I and II by using the Kaplan-Meier method. Baseline predictors of perioperative and late deaths were identified by initially performing univariate Cox proportional-hazards analysis on candidate clinical and laboratory variables (7). Variables that were univariately significant (on the basis of a threshold of P 0.15) were entered stepwise in a multivariable logistic regression model to confirm independent predictive value. A P value less than 0.05 was considered statistically significant. Results Clinical Correlates Of 135 patients, 36 (27%) had pericardial calcification on chest radiography. In all but 2 cases, calcium was identified before the diagnosis of constriction was confirmed. The causes of calcific constrictive pericarditis are listed in Table 1. In most patients with pericardial calcification (67%), the cause could not be identified and the disorder was considered idiopathic. Calcified pericardium was significantly less common in patients who had constriction after cardiac surgery, but its incidence in patients with other specific causes of constriction did not differ between groups. Miscellaneous causes of calcified pericardium included asbestos exposure (1 patient) and post-traumatic pericarditis (2 patients). Table 1. Clinical Profile and Causes of Calcific Constrictive Pericarditis (Group I) and Noncalcific Constrictive Pericarditis (Group II) in 135 Patients Salient clinical features of both patient groups are given in Table 1. No significant relation was seen between calcification and age (P>0.2). At least 1 year before presentation for our study, 18 patients had chest radiographs that showed pericardial calcification. The median duration of symptoms was 33.2 months in group I and 8.4 months in group II (P<0.001). The most common presentation, dyspnea or congestive heart failure, occurred in approximately two thirds of the patients in both groups. None of the patients in group I were admitted in cardiac tamponade; however, cardiac tamponade was seen at presentation in 7% of patients in group II as a manifestation of effusive-constrictive pericarditis. The groups did not differ significantly in New York Heart Association functional class. A pericardial knock was auscultated more frequently in group I than in group II, but a friction rub was noted more frequently in group II. In group I, arrhythmia was more common: Thirty-one percent of patients had atrial fibrillation on initial electrocardiography compared with 5% of patients in group II (P<0.001) (Table 1). Calcific pericarditis was significantly more common in patients with atrial fibrillation or flutter; it occurred in 14 of 22 such patients (64%) compared with 18 of 105 patients in sinus rhythm (17%) (odds ratio, 8.46 [95% CI, 5.05 to 14.18]; P<0.001). Investigations for Granulomatous Infection Mycobacterial cultures of excised pericardium were obtained from 54 of 132 patients (41%) who had pericardiectomy; cultures were negative in 53 of these patients. In 60 of 132 patients (45%), fungal cultures of pericardial tissue were negative. These cultures were also performed in 40 of 71 patients (56%) with acute pericarditis, suspected infection, or constrictive pericarditis of indeterminate cause. Histologic examination of the pericardium was performed for 130 of 135 patients (96%). Noncaseating granuloma formation was found in 1 patient in group II who had acute pericarditis, an anergic tuberculin test (10 units of purified protein derivative [PPD]), and negative tuberculous and fungal cultures. Of 19 patients who had PPD inoculation at our institution or elsewhere, 16 had negative results on histologic examination. The PPD test result was positive in 3 patients, all of whom were in group I. Chest radiography showed a Ghon complex in 1 of these patients; however, the other 2 patients did not have clinical, radiologic, culture-based, or histologic evidence of pulmonary or extrapulmonary tuberculosis. On the basis of serologic testing, 1 patient in group II was considered to have previous infection with Histoplasma species. None of the 135 patients had previously been treated with combination antituberculous chemotherapy; 1 patient with a noncalcified pericardium received prophylactic isoniazid for 1 year after exposure. Radiologic Studies Anteroposterior and lateral chest radiographs were available for review for all but 2 patients. Pericardial calcification was usually better appreciated in lateral radiographs than in frontal radiographs. The regional occurrence of pericardial calcification is shown in Table 2. Calcification predominated over the inferior (diaphragmatic) and anterior (right ventricular) surface of the heart. Apical calcification was not uncommon but occurred in the absence of calcium in other regions in only 1 patient. Calcification overlying the left atrium was unusual (Figure 1). The densest calcification was seen in 34 patients. Among these 34 patients, calcification occurred over the inferior or anterior aspect of the cardiac silhouette in 30 (88%), in the atrioventricular grooves in 2 (6%), and in miscellaneous sites in 2 (6%). Computed tomography demonstrated pericardial calcification in 25 of 85 patients. Calcification was present in all 13 patients in group I (100%) and in 12 of 72 patients in group II (17%). Table 2. Distribution of Radiographic Calcification in 34 Patients with Calcific Constrictive Pericarditis Figure 1. Radiographs of patients with calcification. Top. Middle. Bottom. Echocardiography Echocardiography was performed in 28 patients in group I (78%) and 95 patients in group II (96%). Differences in cardiac dimensions between the groups are shown in Table 3. The atrial and inferior vena cava were significantly larger in group I patients. The groups did not differ with respect to ventricular size or left ventricular ejection fraction. Table 3. Echocardiographic Measurements in Patients with Calcific Constrictive Pericarditis (Group I) and Patients with Noncalcific Constrictive Pericarditis (Group II) Pericardial Calcification as a Diagnostic Clue Pericardial constriction was suspected in 43 patients before they were referred to our institution for further management. After excluding these patients and the 26 patients who were self-referred, 66 patients remained. Of these 66 patients, 25 received a diagnosis of congestive heart failure of uncertain cause, 9 received a diagnosis of liver disease, 3 received a diagnosis of restrictive cardiomyopathy, 22 received a diagnosis of other miscellaneous conditions, and 7 received a diagnosis of unknown causes. Despite the presence of calcification on radiography, constrictive pericarditis was not clinically suspected in 1

PERICARDIAL THICKNESS MEASURED WITH TRANSESOPHAGEAL ECHOCARDIOGRAPHY: FEASIBILITY AND POTENTIAL CLINICAL USEFULNESS

OBJECTIVES This study assessed the reliability of transesophageal echocardiographic measurements of pericardial thickness and the potential diagnostic usefulness of this technique. BACKGROUND Transthoracic echocardiography cannot reliably detect thickened pericardium. The superior resolution achieved with transesophageal echocardiography should allow better pericardial definition. METHODS Pericardial thickness measured at 26 locations in 11 patients with constrictive pericarditis who underwent intraoperative transesophageal echocardiography was compared with pericardial thickness measured with electron beam computed tomography. Intraobserver and interobserver variabilities were determined. Pericardial thickness was then measured in 21 normal subjects. With these values as a guide, two observers reviewed 37 transesophageal echocardiographic studies to determine whether echocardiographic measurement of pericardial thickness could be used to distinguish diseased from normal pericardium. RESULTS The correlation between echocardiographic and computed tomographic measurements (r > or = 0.95, SE < or = 0.06 mm, p < 0.0001) was excellent. The +/-2 SD limits of agreement were +/-1.0 mm or less for pericardial thickness < 5.5 mm and +/-2.0 mm or less for the entire range of thicknesses. Intraobserver and interobserver agreements were good. Mean normal pericardial thickness was 1.2 +/- 0.8 mm (+/-2 SD) and did not exceed 2.5 mm. Pericardial thickness > or = 3 mm on transesophageal echocardiography was 95% sensitive and 86% specific for the detection of thickened pericardium. CONCLUSIONS Measurement of pericardial thickness with transesophageal echocardiography is reproducible and should be a valuable adjunct in assessing constrictive pericarditis.

Growth differentiation factor 15, ST2, high‐sensitivity troponin T, and N‐terminal pro brain natriuretic peptide in heart failure with preserved vs. reduced ejection fraction

Growth differentiation factor 15 (GDF15), ST2, high‐sensitivity troponin T (hsTnT), and N‐terminal pro brain natriuretic peptide (NT‐proBNP) are biomarkers of distinct mechanisms that may contribute to the pathophysiology of heart failure (HF) [inflammation (GDF15); ventricular remodelling (ST2); myonecrosis (hsTnT); and wall stress (NT‐proBNP)].

Left ventricular systolic and diastolic function after pericardiectomy in patients with constrictive pericarditis: Doppler echocardiographic findings and correlation with clinical status.

OBJECTIVES The study assessed changes in left ventricular systolic and diastolic function after pericardiectomy in patients with constrictive pericarditis and correlated postoperative Doppler echocardiographic findings with clinical status. BACKGROUND Despite the efficacy of pericardiectomy, some patients with constrictive pericarditis fail to improve postoperatively. Data on serial evaluation of systolic and diastolic function after pericardiectomy and its relation to clinical status are not available. METHODS From 1985 to 1995, a total of 58 patients with constrictive pericarditis underwent pericardiectomy and had at least one follow-up Doppler echocardiographic study with a respirometer: 23 patients had one examination within 3 months postoperatively, 19 had a study within 3 months and another one more than 3 months postoperatively, and 16 had one study more than 3 months postoperatively. RESULTS In the early postoperative period, diastolic function was normal in 17 patients (40.5%), restrictive in 17 (40.5%), and constrictive in 8 (19%). Among 19 patients who had serial Doppler echocardiography, in 2 patients with restrictive physiology and 5 with constrictive physiology the results had become normal, and 1 patient who had had constrictive physiology had restrictive findings. In late follow-up, left ventricular end-diastolic diameter increased compared with preoperative measurement (p = 0.0009). Diastolic filling pattern at late follow-up was normal in 20 patients (57%), restrictive in 12 (34%) and constrictive in 3 (9%). There was a significant relationship between diastolic filling patterns and symptomatic status (chi2 = 20.9, p < 0.0001). Patients with persistent abnormal diastolic filling on Doppler echocardiography had had symptoms for a longer time preoperatively than did patients with normal diastolic physiology (p = 0.0471). CONCLUSIONS Diastolic filling characteristics remain abnormal in a substantial number of patients with constrictive pericarditis after pericardiectomy. These abnormalities may resolve gradually but can persist. Diastolic filling abnormalities after pericardiectomy correlate well with clinical symptoms and tend to occur in patients who have had symptoms longer preoperatively. This finding supports the recommendation that pericardiectomy be performed promptly in symptomatic patients with constrictive pericarditis.