Lisa A. Mendes

Right ventricular dysfunction: An independent predictor of adverse outcome in patients with myocarditis

To assess the predictive value of right ventricular systolic function in patients with active myocarditis, the echocardiograms of 23 patients with biopsy-confirmed myocarditis were reviewed. Right ventricular systolic function was evaluated qualitatively and quantitatively by descent of the right ventricular base. Patients were divided into those with normal right ventricular function, in whom right ventricular descent was 1.9 +/- 0.1 cm, and those with abnormal right ventricular function, in whom right ventricular descent was 0.8 +/- 0.1 cm (p < 0.001). There were no differences between the two groups in age, duration of symptoms, baseline hemodynamics, or histologic assessment. Initial left ventricular ejection fraction was significantly lower in patients with depressed right ventricular function (27.5 +/- 4.9%) compared with that in patients with normal right ventricular function (47.5 +/- 6.3%) (p = 0.01). The likelihood of an adverse outcome, defined as death or need for cardiac transplantation, was greater in patients with abnormal right ventricular function (right ventricular descent < or = 1.7 cm) than in patients with normal right ventricular function (right ventricular descent > 1.7 cm) (p < 0.03). Multivariate analysis revealed that right ventricular dysfunction as quantified by right ventricular descent was the most powerful predictor of adverse outcome.

Right coronary artery stenosis : an independent predictor of atrial fibrillation after coronary artery bypass surgery

OBJECTIVESnThis study attempted to determine the importance of severe proximal right coronary artery disease as a predictor of atrial fibrillation in patients after coronary artery bypass surgery.nnnBACKGROUNDnStudies in patients undergoing noncardiac surgery have suggested that ischemia in the right coronary artery distribution is associated with a high incidence of atrial fibrillation. However, the importance of right coronary artery disease as a predictor of atrial fibrillation after bypass surgery is unknown.nnnMETHODSnThe occurrence of sustained postoperative atrial fibrillation was studied prospectively in 168 consecutive patients undergoing coronary artery bypass grafting. Patients were followed up postoperatively until discharge. Severe right coronary artery stenosis was defined as > or = 70% lumen narrowing.nnnRESULTSnOf 104 patients with proximal or mid right coronary artery stenosis, 45 (43%) had atrial fibrillation postoperatively compared with 12 (19%) of the 64 patients without significant right coronary disease (p = 0.001). Univariate predictors of atrial fibrillation included right coronary artery stenosis (p = 0.001), advancing age (p = 0.0001) and lack of beta-adrenergic blocking agent therapy after bypass surgery (p = 0.0004). Multivariate adjusted risk of developing atrial fibrillation after bypass surgery increased with the presence of severe right coronary artery disease (odds ratio 3.69, 95% confidence interval [CI] 1.61 to 8.48), advancing age (odds ratio 2.24/10 years, CI 1.48 to 3.41) and male gender (odds ratio 2.36, CI 1.01 to 5.49). The use of beta-blockers postoperatively was associated with a protective effect (odds ratio 0.4, CI 0.17 to 0.80).nnnCONCLUSIONSnThe presence of severe right coronary artery stenosis is an independent and powerful predictor of atrial fibrillation after coronary artery bypass surgery. In association with age, gender and postoperative beta-blocker therapy, these variables can be used to identify patients at increased risk for developing this arrhythmia.

Congestive heart failure in patients with coronary artery disease: the gender paradox.

To determine whether the increased prevalence of congestive heart failure in women compared with men undergoing diagnostic cardiac catheterization is the result of a difference in the left ventricular pressure/volume relation, we retrospectively compared the clinical characteristics, left ventricular ejection fraction, and end-diastolic pressure and volume in 586 women and 1081 men undergoing diagnostic coronary angiography and left ventriculography. In comparison with men, women were older (63 vs 60 years; p = 0.0001) and had more hypertension (41% vs 31%; p = 0.0001), diabetes (18% vs 12%; p = 0.003), and symptoms of congestive heart failure (13% vs 10%; p = 0.05). In spite of this, women had a better mean left ventricular ejection fraction (61% vs 56%; p = 0.0001) and less prevalent three-vessel disease (23% vs 34%; p = 0.0001). Left ventricular end-diastolic volume index was smaller in women compared with men (73 vs 79 ml/m2; p = 0.0001) in spite of having similar left ventricular end-diastolic pressure. When patients were stratified according to left ventricular end-diastolic pressure, women had a significantly smaller end-diastolic volume than men did when left ventricular end-diastolic pressure was > or = 18 mm Hg (74 vs 86 ml/m2; p = 0.0001). In a multivariate analysis, female sex remained an independent predictor of congestive heart failure (odds ratio 1.72, 95% confidence interval 1.11 to 2.66, p = 0.02). This study suggests that diastolic dysfunction is one mechanism for the paradox of more frequent heart failure symptoms in spite of better preserved left ventricular systolic function in women. Sex appears to influence the pattern of myocardial dysfunction in patients with known or suspected coronary artery disease, but the basis for this observation remains speculative.

Right ventricular dilation in primary amyloidosis: An independent predictor of survival

This study was designed to characterize the geometry and function of the right ventricle and its prognostic significance in patients with primary (AL) cardiac amyloidosis. AL amyloidosis is an infiltrative systemic disease that can result in thickening of heart structures and rapidly progressive congestive heart failure due to restrictive ventricular physiology and eventual systolic dysfunction. Thirty-seven patients with AL amyloid heart involvement and 20 normal control subjects were evaluated using 2-dimensional and Doppler echocardiography. Based on the ratio of left-to-right end-diastolic ventricular chamber areas, patients were classified into 2 groups: 25 patients with disproportionate right ventricular (RV) dilation (left ventricular to RV ratio < or = 2) and 12 with a ventricular area ratio > 2. Patients with a relatively dilated right ventricle (ratio < or = 2) had a shorter median survival (4 months) compared with patients with an area ratio > 2 (10 months, p <0.003). Of multiple clinical, echocardiographic, and Doppler features entered into a multifactorial model, a ventricular area ratio < or = 2 remained the only independent predictor of survival. Patients with AL amyloid heart disease represent a heterogeneous population with regard to both prognosis and the relative degree of right to left ventricular dilation. RV dilation in patients with amyloid heart disease appears to be associated with more severe involvement and is associated with a very poor prognosis with a median survival of only 4 months.

Increased left ventricular diastolic chamber stiffness immediately after coronary artery bypass surgery

OBJECTIVESnThe aim of this study was to assess the incidence and severity of left ventricular diastolic dysfunction immediately after coronary artery bypass surgery by utilizing simultaneous transesophageal echocardiographic and hemodynamic monitoring.nnnBACKGROUNDnLeft ventricular diastolic dysfunction has been documented after coronary bypass surgery, but its measurement has been technically difficult to acquire and limited by dependence on loading conditions.nnnMETHODSnEnd-diastolic pressure-area curves were constructed before and immediately after coronary bypass surgery in 20 patients. Transesophageal echocardiographic images at the midpapillary level of the left ventricle and hemodynamic data were recorded. Volume status was manipulated to alter loading conditions, and multiple measurements were taken at each loading condition.nnnRESULTSnDiastolic function worsened in all patients, as manifested by a postoperative leftward shift of the end-diastolic pressure-area curve. At a comparable preload, mean end-diastolic area +/- SEM decreased by 15% from 17.6 +/- 0.8 to 14.9 +/- 0.8 cm2 postoperatively (p = 0.0001).nnnCONCLUSIONSnLeft ventricular diastolic chamber stiffness frequently increases immediately after coronary artery bypass surgery. Simultaneous hemodynamic and transesophageal echocardiographic monitoring, through the construction of end-diastolic pressure-area curves, is a useful method to evaluate diastolic function and guide management after cardiac surgery.

Resolution of Heart Failure in Patients with AL Amyloidosis

AL (primary) amyloidosis is a plasma cell dyscrasia that results in systemic disease. In patients who have this condition, cardiac involvement indicates the worst outcome, and the development of clinical heart failure is associated with a median survival of less than 6 months [1]. Trials of treatment for AL amyloidosis have had disappointing results; they show only modest benefit from the currently available therapies [2, 3]. This reflects the limited success obtained to date in slowing or turning off production of light-chain fragments, which are the precursors of amyloid deposition. In a few patients, the signs and symptoms caused by amyloid infiltration appear to have been reversed. Almost all of the information on these patients has been presented in individual case reports that detail renal [4], gastrointestinal [5], or neurologic recovery [6]. Long-term survival in patients who have AL amyloidosis that affects the heart is extremely unusual [7, 8], and no echocardiographic details have been reported for patients in whom cardiac symptoms of AL amyloidosis have been alleviated. We describe the clinical features of three patients whose cardiac symptoms of amyloidosis were substantially alleviated, and we correlate this alleviation with echocardiographic features and objective evidence of disease activity. Methods All patients were examined by a cardiologist at initial and subsequent evaluations. Twelve-lead and 24-hour Holter electrocardiography, transthoracic echocardiography, and Doppler echocardiography were done. Disease activity was determined on the basis of bone marrow plasma cell percentages, evidence of monoclonal bands on serum protein electrophoresis, and the presence of light chains in serum or urine. Echocardiograms were read by blinded investigators to assess features of amyloid involvement. Left ventricular mass was calculated, and the ratio of voltage to mass was derived from the electrocardiographic voltage for the limb leads (mean QRS amplitude in leads I, II, III, aVF [augmented V lead, left leg], and aV (L) [augmented V lead, left arm]) divided by the left ventricular mass [9]. Results Of 249 patients with AL amyloidosis, 140 (56%) had congestive heart failure (median predicted survival, 7 months). Of these 140 patients, 78 (56%) received colchicine alone and 56 (40%) received melphalan (5 received high-dose melphalan therapy and autologous stem cell rescue). Six patients (4%) received no treatment. Heart failure was alleviated in 3 of the 140 patients who had congestive heart failure (2.1%), and all 3 of these patients had received melphalan as part of their treatment regimen. None of the 78 patients who had received colchicine alone had clinical alleviation of heart failure (P = 0.07). One of the 3 patients whose heart failure was alleviated is described below, and the clinical details from this patient and from the other two patients are shown in Table 1. Table 1. Clinical Features of, Functional Status of, and Therapies for Patients Case Reports Patient 1 A previously healthy 52-year-old man presented with a 1-year history of increasing shortness of breath on exertion. A diagnosis of AL amyloidosis was suspected on the basis of free light chains in the serum. Examination of the bone marrow showed that 7% of the cells were plasma cells (Table 2). On examination, the jugular venous pressure was markedly elevated (15 cm), and leg edema and hepatomegaly were seen. Increasingly severe heart failure developed, and the patient had dyspnea on minimal exertion. Cardiac catheterization showed normal coronary arteries, but during preparations for a right ventricular biopsy, the patient developed profound bradycardia and electromechanical dissociation that required open-chest cardiac massage. Pleural biopsy at this time confirmed amyloidosis. After further episodes of syncope, which occurred without warning, a permanent pacemaker was implanted and the symptoms resolved. Therapy for heart failure included 80 mg of furosemide and 5 mg of metolazone per day. An echocardiogram showed a small left ventricular cavity with mild wall thickening and increased echogenicity compatible with heart disease due to AL amyloidosis (Table 2). Table 2. Values from Laboratory and Cardiovascular Evaluations at Initial and Latest Assessments During the next 8 months, the patients condition continued to deteriorate. He had increasing heart failure and recurrent pleural effusions, and admission to a terminal care hospice was arranged. Throughout this period, the patient received a daily regimen of melphalan and prednisone to a total melphalan dosage of 860 mg per day. Thereafter, the symptoms of heart failure began to gradually resolve (Table 1). Cardiovascular examination 6 years after initial evaluation showed resolution of the edema and hepatic congestion with persistent mild elevation of jugular venous pressure. The patients heart failure, initially New York Heart Association (NYHA) class IV, had improved to NYHA class I. The patient has returned to full-time employment. At an evaluation done 82 months after the initial symptoms of heart failure (80 months after tissue diagnosis), no light chains were detectable in the patients serum or urine and the results of a bone marrow examination were normal. These findings suggest that the disease was in remission or that the patient had been cured (Table 2). Patients 2 and 3 Detailed data for patients 2 and 3 are given in Table 1 and Table 2. Briefly, patient 2 had NYHA class IV heart failure at presentation and required large doses of diuretics and repeated thoracenteses. Her symptoms completely resolved after she received several courses of chemotherapy, and she returned to full-time employment 24 months after receiving the diagnosis of amyloidosis. Patient 3 had evidence of severe right ventricular infiltration with amyloid and required repeated thoracenteses for right heart failure. Chemotherapy was associated with gradual alleviation of symptoms, cessation of thoracenteses, and a decrease in previously marked macroglossia. Patient 3 is now free of heart failure, 65 months after receiving the diagnosis of amyloidosis. Discussion We describe 3 patients with documented AL amyloidosis and congestive heart failure whose symptoms were clearly alleviated. The rarity of such alleviation is apparent from the fact that these 3 patients made up only 2.2% of 140 consecutive patients who had congestive heart failure caused by AL amyloidosis. All 3 had received multiple courses of melphalan. In contrast, no improvement was seen in any of the patients who had received colchicine alone. This suggests that chemotherapy was responsible for the improvement in these patients, and this is further supported by a previously described survival difference between a small group of patients who had AL amyloidosis and heart failure and were treated with chemotherapy and a group of patients with the same conditions who were treated with colchicine alone [2, 3]. Only a few reports of improvement in patients with AL amyloidosis and cardiac involvement have been published [8, 10, 11]. In a review of 153 patients, Gertz and colleagues [8] briefly mention 2 patients with such improvement, but they provide no laboratory or echocardiographic details. A single patient described by Brown and Walls [11] also appears to have recovered from heart failure, but the evidence for this is confounded by the fact that the patient was in atrial fibrillation at the time of diagnosis and was in sinus rhythm when heart failure resolved. All 3 of these patients also received chemotherapy. The resolution of symptoms seen in our patients was accompanied by the disappearance of light chains from serum and urine, suggesting either disease remission or cure. The eventual resolution of symptoms was characterized in all three cases by an initial worsening despite the initiation of therapy. Inconsistencies between clinical improvement and the lack of evidence for a reduction in organ involvement with amyloidosis have been described in the nephrotic syndrome, in which persistent amyloid deposition is frequently seen on repeated renal biopsies [12]. Notably, in all reported cases, resolution of the nephrotic syndrome was associated with the disappearance of light chains [12]. Furthermore, all of these patients had been treated with melphalan. These observations suggest that something other than the simple physical presence of amyloid in the kidney may be responsible for the heavy proteinuria; light-chain toxicity in both kidney and muscle has been proposed [13-16]. The use of melphalan and prednisone has modestly improved the prognosis of patients with AL amyloidosis [17, 18], even those with congestive heart failure [3, 17]. Our three cases may only be examples of the most dramatic responses to chemotherapy, and we cannot exclude the possibility that disease progression was slowed in other patients with heart failure who received chemotherapy, even though these patients ultimately died of cardiac disease. The number of courses of chemotherapy received appears to be critical to achieving disease regression; because the median period of treatment required for a clinical response is 1 year [8], most patients with cardiac symptoms of amyloidosis probably do not survive long enough to receive an effective therapeutic regimen of melphalan. We show that heart failure can be reversed in some patients with AL amyloidosis, and we suggest that more intensive chemotherapysuch as that recently developed using high-dose melphalan and autologous stem cell rescuemight increase the number of patients responding to therapy. Dr. Skinner: Arthritis Research Center, Boston University School of Medicine, Boston, MA 02118.

Right Ventricular Thrombus: An Unusual Manifestation of Behçet's Disease

Behcets disease is a chronic multisystem illness in which cardiac involvement is a rare manifestation. In this unusual case a young man had symptoms that primarily related to recurrent right ventricular thrombi and pulmonary thromboemboli. Transesophageal echocardiography was useful in documenting the presence of intracardiac thrombus and establishing the diagnosis.

Cardiogenic seizure with bradyarrhythmia: Documentation of the mechanism during asystole

Fig. 3. Atria1 extrastimulus study after administration of sotalol at BCL 700 msec. Upper panel, Normal conduction of premature beat with a Hz-V:! interval of 90 msec. Middle panel, As HI-HZ interval shortens by 10 msec to 505, premature beat is conducted with left BBB pattern and Hz-V2 of 100 msec. Lower panel, Further shortening of HI-HZ interval to 490 msec causes sudden jump of HY-VZ interval to 220 msec with right. BBB morphology of conducted beat.

1019-28 Retrograde Cardioplegia Increases Diastolic Chamber Stiffness After Coronary Artery Bypass Surgery

We have previously shown that diastolic dysfunction is frequent immediately after CABG. Although combined antegrade and retrograde cardioplegia (A + R) may improve myocardial protection, it can also lead to extracellular edema and microvaSCUlar injury. To assess postCABG diastolic function after A + R cardioplegia, volume manipUlation was used to create pressure-area curves before and after CABG in 20 pts. LV end diastOlic area (EDAREA) was measured by transesophageal echocardiography as an index of end diastOlic volume, and plotted against the PCWP as an estimate of mean LV diastOlic pressure. A smaller EDAREA at a similar PCWP postCABG reflects a leftward shift in the pressure-area curve and increased LV diastolic chamber stiffness. A (nxa0=xa014) A+R (nxa0=xa06) p EF(%) 52xa0±xa04 56xa0±xa04 NS Wall thickness (mm) 9.9xa0±xa00.1 9.3xa0±xa00.3 NS Bypass (min) 80xa0±xa05 74xa0±xa07 NS Pre-Post Δ PCWP (mmHg) 1xa0±xa01 0xa0±xa01 NS Pre-Post Δ EDAREA (%) -12.4xa0±xa023 -22.5xa0±xa030 0.02 Increased LV diastolic chamber stiffness occurred in all pts postCABG, but was more pronounced with both antegrade and retrograde cardioplegia. Conclusion After CABG, combined A + R cardioplegia is associated with a more prominent increase in diastolic chamber stiffness than antegrade cardioplegia alone. Recognition of worsening diastolic function with A + R may be important for optimal pt management postCABG.

726-3 Functional Mitral Regurgitation Correlates with Incomplete Mitral Valve Closure not Left Ventricular Sphericity in Active Myocarditis

Incomplete mitral valve (MV) closure and LV sphericity correlates with functional MR in chronic dilated cardiomyopathy. To assess the mechanism of MR in active myocarditis (M) echocardiograms performed within 5.7xa0±xa01.2 days of initial RV biopsy in 27 pts with histologically proven M enrolled in the Myocarditis Treatment Trial were analyzed. M pts were stratified into those with mild MR (≤1 +, nxa0=xa014) and moderate MR (≥2+, nxa0=xa013). LV volume (vol) was measured and a sphericity index (SI) calculated. A value approaching 1 represents increased sphericity. Mitral annular (MA) diameter (d), the distance (DIS) between MV leaflet coaptation and MA plane, and the area enclosed by MVand MA (MVarea) were measured and compared to 20 normal controls. MAd (em) DlS(cm) MVarea (cm 2 ) LVvol (cc/m 2 ) SI Control 23xa0±xa002 0.32xa0±xa0013 034xa0±xa0013 49.5xa0±xa079 0.36xa0±xa00.05 ≤1+ MR 3.1xa0±xa00.4 * 0.60xa0±xa00.14 * 1.2xa0±xa00.45 * 79.7xa0±xa028.9 * 0.47xa0±xa00.10 * ≥2+ MR 3.9xa0±xa00.5 * 0.96xa0±xa00.18 * 23xa0±xa00.64 * 78.3xa0±xa029 * , † 0.48xa0±xa00.09 * , † * p l 0.0001 compared to control † p = N5 compared to ≤lxa0+xa0MR Conclusion In active M, functional MR does not correlate with increasing LV sphericity. Incomplete MV closure and MA dilatation are more important correlates of MRseverity.