Losartan treatment and left ventricular filling during volume loading in patients with dilated cardiomyopathy

Background Patients with mild heart failure show a reduction in preload reserve mechanism during volume expansion. At this time, the effects of volume expansion on left ventricular (LV) diastolic filling in this subset of patients have not been well characterized. Methods We evaluated the effects of acute volume loading on Doppler parameters of LV filling in 10 healthy control subjects and in 12 patients with idiopathic dilated cardiomyopathy (DCM). In patients with DCM, the effects of losartan on diastolic adaptation to volume load were also investigated. Results During volume loading, the healthy control subjects showed a decrease in isovolumic relaxation time (F = 5.3, P < .05) but an increase in the LV peak filling rate (F = 52.9, P < .001) and velocity time integral of both systolic (F = 72.8, P < .001) and diastolic (F = 4.6, P < .05) pulmonary venous flow. In patients with DCM, isovolumic relaxation time decreased more than in control subjects (F = 8.1, P < .01), and the deceleration time of the early mitral wave was reduced (F = 26.3, P < .001). Furthermore, the duration of pulmonary venous flow reversal exceeded that of mitral flow at atrial contraction (F = 28.5, P < .001). After treatment with losartan, the deceleration time of early mitral wave remained unchanged, and the duration of pulmonary venous flow reversal at atrial contraction did not exceed that of mitral flow; thus, a significant treatment effect was detectable (F = 5.6, P < .05; and F = 6.6, P <.05, respectively). Conclusions Control subjects respond to volume load with enhancement in early LV filling, whereas patients with DCM show an increase of LV filling pressure. Diastolic adaptation to volume load improves in patients with DCM after treatment with losartan. (Am Heart J 2002;143:433-40)     

Serum glucose and lipid levels in adult congenital heart disease patients

Atherosclerosis has been correlated with known cardiovascular risk factors such as serum glucose or lipid levels. Because congenital heart disease patients tend to survive until adulthood, atherosclerosis has also become a matter of concern in these patients. One hundred fifty-eight congenital heart disease patients and 152 patients selected at random from the population were studied and compared to determine serum glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, and triglycerides levels. Both groups had similar socioeconomic status levels and the same environmental influences. Significant differences were seen between congenital heart disease patients and the control group, after sex, age, and body mass index adjustment, in fasting plasma glucose (97.7 [94.2-101.2] vs 86.9 [83.2-90.7], P < .001), total cholesterol (171.5 [165.7-177.3] vs 199.8 [90.7-206.0], P < .001), LDL cholesterol (103.9 [98.8-108.8] vs 123.8 [118.5-129.1], P < .001), and high-density lipoprotein cholesterol (48.1 [46.2-50.0] vs 54.2 [52.1-56.2], P < .001) levels. Nonsignificant differences were seen in triglycerides concentrations. Those patients with ventricular septal defect, coarctation of the aorta, and cyanosis had the lowest total cholesterol and LDL cholesterol concentrations. Congenital heart disease patients have lower plasma cholesterol concentrations and higher serum glucose levels than noncongenital ones.     

Long-term outcome and the use of revascularization in patients with heart failure,suspected ischemic heart disease,and large reversible myocardial perfusion defects

Background The potential role of coronary revascularization in the management of patients with congestive heart failure and suspected ischemic heart disease remains to be defined. Myocardial perfusion imaging can identify patients with ischemic heart disease as the etiology for left ventricular dysfunction who might benefit from revascularization. Methods We retrospectively identified heart failure patients with suspected ischemic heart disease who had large reversible perfusion defects to determine their long-term outcome and rate of revascularization. The study group consisted of 77 patients with congestive heart failure, left ventricular ejection fraction <45%, and suspected ischemic heart disease who underwent myocardial perfusion imaging during the period of January 1, 1991, to December 31, 1997, and had large reversible perfusion defects. Results The 5-year mortality rate was 57.6%. The revascularization rate was only 13% for 5 years of follow-up. The number of patients undergoing revascularization was too small to assess its impact on outcome. Conclusion These results indicate a high 5-year mortality rate and a low utilization of coronary revascularization in patients with heart failure and large reversible perfusion defects. The low rate of revascularization reflects at least in part the absence of the generalizability of the existing literature to the optimal means of treating patients with heart failure and myocardial ischemia and points to the need for a randomized clinical trial. (Am Heart J 2002;143:904-9.)     

Elevated serum uric acid levels are associated with diastolic dysfunction in patients with dilated cardiomyopathy

Objective To assess whether serum uric acid, which is a marker of impaired oxidative metabolism, might correlate with left ventricular systolic and diastolic dysfunction in patients with chronic heart failure (CHF). Background Uric acid levels, which are frequently elevated in patients with CHF, correlate with leg vascular resistance. The effects of elevated levels of uric acid on cardiac function in patients with CHF have never been evaluated. Methods We studied 150 outpatients with CHF who came to our heart failure clinic. Patients underwent a complete echo-Doppler examination, with measurement of mitral E wave and mitral A wave velocities, E/A ratio, E wave deceleration time (DtE), left ventricular volumes, ejection fraction, and stroke volume. A restrictive mitral filling pattern (RMFP) was defined as either E/A ratio >2 or E/A >1 and DtE <140 milliseconds. Results Mean age was 62.2 ± 7.8 years (86% male); 24 patients (16%) had an RMFP. Patients with an RMFP had significantly higher uric acid levels compared with patients without RMFP (0.48 ± 0.14 mmol/L vs 0.38 ± 0.08 mmol/L, respectively, P < .001). Uric acid levels correlated significantly with mitral E wave velocity (r = .22, P < .01), E/A ratio (r = .21, P < .05), DtE (r = .26, P < .01), and RMFP (P = .0001). There was no correlation between uric acid and left ventricular volumes, ejection fraction, or stroke volume. In a multivariate model, uric acid predicted DtE independently of renal function, diuretic dose, and left ventricular volumes. Conclusion Elevated uric acid levels are associated with diastolic dysfunction in CHF. Xanthine oxydase inhibition in patients with CHF might theoretically result in an improvement of diastolic function. (Am Heart J 2002;143:1107-11.)     

Rationale and design of a study assessing treatment strategies of atrial fibrillation in patients with heart failure: the Atrial Fibrillation and Congestive Heart Failure (AF-CHF) trial

Background Nonrandomized studies suggest that atrial fibrillation is independently associated with increased mortality in patients with heart failure. Whether restoring and maintaining sinus rhythm will have a beneficial impact on cardiovascular mortality in patients with heart failure has never been tested in an adequately powered randomized trial. Objective The primary objective of the Atrial Fibrillation and Congestive Heart Failure (AF-CHF) trial is to determine whether restoring and maintaining sinus rhythm significantly reduces cardiovascular mortality compared with a rate-control strategy in patients with atrial fibrillation and CHF. Methods AF-CHF is a prospective multicenter trial (109 centers in Canada, United States, South America, Europe, and Israel), that will randomize 1450 patients with CHF with left ventricular ejection fraction ≤35% and atrial fibrillation to 1 of 2 treatment strategies: (1) rhythm control with the use of electrical cardioversion combined with antiarrhythmic drugs (amiodarone or other class III agents), (2) rate control with the use of β-blockers, digoxin, or pacemaker and AV nodal ablation. Cardiovascular mortality is the primary end point and the intention-to-treat approach the primary method of analysis. We anticipate an 18.75% 2-year cardiovascular mortality in the rate control arm with a 25% mortality reduction in the rhythm control group. Results As of August 13, 2002, 334 patients have been enrolled from 68 participating centers. Enrollment is expected to be concluded in May 2003 with a minimum follow-up of 2 years. Conclusion The results of this trial should provide definitive information concerning 2 widely applicable treatment strategies of atrial fibrillation in a large cohort of patients with CHF. (Am Heart J 2002;144:597-607.)     

Challenges and Future Opportunities for Transcatheter Aortic Valve Therapy

Background

Transcatheter aortic valve replacement (TAVR) is a novel less-invasive therapy for high-risk patients with severe aortic stenosis (AS). Despite the impressive clinical growth of TAVR, there are many challenges as well as future opportunities.

Results

The heart valve team serves as the central vehicle for determining appropriate case selection. Considerations which impact clinical therapy decisions include frailty assessments and defining clinical “futility”. There are many controversial procedural issues; choice of vascular access site, valve sizing, adjunctive imaging, and post-dilatation strategies. Complications associated with TAVR (strokes, vascular and bleeding events, para-valvular regurgitation, and conduction abnormalities) must be improved and will require procedural and/or technology enhancements. TAVR site training mandates a rigorous commitment to established society and sponsor guidelines. In the future, TAVR clinical indications should extend to bioprosthetic valve failure, intermediate risk patients, and other clinical scenarios, based upon well conducted clinical trials. New TAVR systems have been developed which should further optimize clinical outcomes, by reducing device profile, providing retrievable features, and preventing para-valvular regurgitation. Other accessory devices, such as cerebral protection to prevent strokes, are also being developed and evaluated in clinical studies.

Summary

TAVR is a worthwhile addition to the armamentarium of therapies for patients with AS. Current limitations are important to recognize and future opportunities to improve clinical outcomes are being explored.     

Cardiac troponin I: a potential marker of exercise intolerance in patients with moderate heart failure

Background In severe heart failure, increased values of cardiac troponins have been detected during decompensation. In this study, we investigated whether an increase of cardiac troponin I can be observed after symptom-limited exercise and after an exercise training session in patients with moderate heart failure. Methods Twenty-seven patients with moderate heart failure (New York Heart Association II-III, ejection fraction 31% ± 8%) were compared with 9 patients with mild heart failure and 10 subjects without heart failure. They underwent a symptom-limited exercise test and a bicycle exercise training session at >80% of maximal heart rate over 20 to 30 minutes. Plasma cTnI levels were measured at baseline, after symptom-limited exercise (hourly for 5 hours), and after training (4 and 10 hours). Results Patients with moderate heart failure showed an increase of cTnI from 37 ± 49 pg/mL to 73 ± 59 pg/mL (P < .001) after symptom-limited exercise. Four patients with moderate and 1 with mild heart failure and normal cTnI values at rest showed an increase of cTnI above 100 pg/mL after acute exercise but not after training. Subjects without heart failure had lower cTnI levels at rest and significantly lower values after symptom-limited exercise and training (P < .05 for each). Conclusion Patients with symptomatic heart failure reveal an increase of cTnI after symptom-limited exercise at levels that indicate minor myocardial damage. The prognostic impact of this finding should, therefore, be further investigated. (Am Heart J 2002;144:351-8)     

Randomized comparison of enoxaparin with unfractionated heparin for the prevention of venous thromboembolism in medical patients with heart failure or severe respiratory disease

Background We compared the efficacy and safety of the low-molecular weight heparin enoxaparin with unfractionated heparin (UFH) for the prevention of venous thromboembolic disease in patients with heart failure or severe respiratory disease. Methods This was a multicenter, controlled, randomized, open study in which patients received either enoxaparin (40 mg once daily) or UFH (5000 IU 3 times daily) for 10 ± 2 days in 64 medical departments in Germany. Patients were stratified and enrolled according to their underlying disease: severe respiratory disease or heart failure. The primary efficacy parameter was a thromboembolic event up to 1 day after the treatment period. Results Of the 665 patients enrolled, 451 patients were able to be evaluated in the primary efficacy analysis. The incidence of thromboembolic events was 8.4% with enoxaparin and 10.4% with UFH. Enoxaparin was at least as effective as UFH, with a 1-sided equivalence region of −4% (90% CI −2.5-6.5, P = .015). Enoxaparin was associated with fewer deaths, less bleeding, and significantly fewer adverse events (45.8% vs 53.8%, P = .044). Conclusions Enoxaparin is at least as effective as UFH in the prevention of thromboembolic events in patients with heart failure or severe respiratory disease. Its beneficial safety profile and once-daily administration is advantageous for inpatient and outpatient use. (Am Heart J 2003;145:614-21.)     

Noninvasive estimation of both systolic and diastolic pulmonary artery pressure from Doppler analysis of tricuspid regurgitant velocity spectrum in patients with chronic heart failure

Background Noninvasive estimation of pulmonary artery systolic and diastolic pressures usually requires the investigation of both tricuspid and pulmonary regurgitant jets and an estimate of right atrial pressure. A new, noninvasive method to obtain pulmonary diastolic pressure (based on the hemodynamic demonstration that right ventricular systolic pressure and pulmonary artery diastolic pressure are equal at the time of pulmonary valve opening) from the analysis of tricuspid regurgitation alone has been described in a small cohort of patients. We sought to verify the accuracy of this method in a large population of patients with heart failure. Methods An estimate of pulmonary artery diastolic pressure was obtained by transposing the pulmonary opening time (from the onset of the R wave on the electrocardiographic tracing to the beginning of pulmonic forward flow on Doppler examination) onto the tricuspid regurgitant velocity curve and calculating the pulmonary artery diastolic pressure value as the pressure gradient between the right ventricle and right atrium at this time. The study group included 86 consecutive patients (64 men, aged 52 ± 11 years) with heart failure (New York Heart Association class ≥II, 94%) who were in stable clinical condition with a chiefly idiopathic (57%), ischemic (24%), or other form (13%) of dilated cardiomyopathy. Noninvasive, right-sided pressures were compared with invasive measurements obtained during right heart catheterization performed within 24 hours. The Bland and Altman graphic method was used together with the calculation of the Lin concordance correlation coefficient and its 95% CI to assess the agreement between hemodynamic and echocardiographic measurements. Results Catheter-derived pulmonary artery systolic pressure ranged from 8 to 119 mm Hg (mean 42 ± 21 mm Hg), pulmonary artery diastolic pressure from 1 to 59 mm Hg (mean 20 ± 11 mm Hg), and right atrial pressure from −5 to 20 mm Hg (mean 6 ± 5 mm Hg). Tricuspid regurgitation was detected in 75 of 86 patients (87%). Pulmonary artery systolic pressure ranged from 13 to 110 mm Hg (mean 44 ± 21 mm Hg); the pressure gradient between the right ventricle and right atrium at time t of the pulmonary valve opening on the tricuspid regurgitation velocity curve was measurable in 70 of 75 (93%) cases and ranged from 3.5 to 64 mm Hg (mean 22 ± 11 mm Hg). Good agreement was observed not only for pulmonary artery systolic pressure but also for pulmonary artery diastolic pressure, based on the analysis of the tricuspid regurgitation velocity jet, with a slight difference between measurements (−1.8 and 0.1, respectively), no evident pattern of point scattering, and a high concordance correlation coefficient that was elicited by the virtually total overlapping of lines on the graph. Overall results were not significantly different whether patients with depressed right ventricular function (right ventricular ejection fraction ≤35%), with a tricuspid regurgitation grade ≥2 and atrial fibrillation were included in the analysis. Conclusions The narrow paired difference for the estimate of pulmonary artery systolic pressure and the even better difference for pulmonary artery diastolic pressure using the tricuspid regurgitation velocity curve analysis indicates that this new method reliably estimates invasive right-sided pressures over a wide range of pressure values in patients with heart failure. The overall good correlation with invasive values indicates that Doppler examination of tricuspid regurgitation alone may provide a simple and comprehensive new method for the noninvasive evaluation of right ventricular and pulmonary hemodynamics in patients with heart failure. (Am Heart J 2002;144:1087-94.)     

An Approach to the Rational Use of Revascularization in Heart Failure Patients

The most common cause of heart failure with reduced ejection fraction (HFrEF) is coronary artery disease. A multitude of factors come into play when deciding whether a patient with HFrEF and coronary artery disease should have coronary artery bypass graft (CABG) surgery, percutaneous coronary intervention, or medical therapy alone. For candidates for percutaneous coronary intervention and CABG, evidence from large registries would suggest that patients with 2-vessel coronary artery diseases and proximal left anterior descending disease and all patients with 3-vessel coronary artery disease do better with CABG. For patients that are candidates for medical therapy with or without CABG, the results of the Surgical Treatment for Ischemic Heart Failure (STICH) trial indicate that with CABG, the reduction of mortality is not statistically significant (hazard ratio [HR], 0.86; P = 0.12). However, CABG is superior in reducing cardiovascular deaths (HR, 0.81; P = 0.05), and the combination of cardiovascular deaths and cardiovascular hospitalizations (HR, 0.74; P < 0.001). Patients undergoing CABG have an upfront risk that is eliminated by 2 years and thereafter do better. The assessment of cardiac viability or reversible ischemia does not appear to be helpful in determining which individuals will improve more with CABG. Patients with severe mitral regurgitation who undergo CABG appear to benefit from simultaneous valve repair but not from the addition of surgical ventricular reconstruction of the left ventricle, although in specific patients this might be considered. The totality of evidence would thus suggest that patients with HFrEF should be evaluated for the possibility of coronary revascularization if they are candidates for CABG.     

Effect of fenfluramine-derivative diet pills on cardiac valves: a meta-analysis of observational studies

Background Fenfluramine-derivative diet pills were withdrawn from the market in 1997 because of an association with valvular regurgitation, but subsequent estimates of the prevalence of this condition have varied widely. We systematically reviewed evidence regarding the prevalence of valvular disease after fenfluramine exposure. Methods We searched multiple databases with multiple search terms. Conference proceedings from 1997 onward were searched by index. Authors of eligible studies were contacted to identify unpublished works. Selection criteria were liberally determined. Ten of the identified 11 articles met these criteria. Reviewers assessed the studies' methodologic quality by use of a standard form to evaluate selection, attrition, performance, and detection bias. The studies were analyzed in 2 groups on the basis of length of exposure (<90 days or >90 days). The Mantel-Haenszel method was used to summarize data. Quantitative and qualitative tests for heterogeneity were performed. Tests for publication bias were also done. Results Tests for heterogeneity were nonsignificant after removing 1 outlier trial. The pooled prevalence of valvular regurgitation meeting Food and Drug Administration criteria (at least mild aortic regurgitation or at least moderate mitral regurgitation) among patients treated for >90 days was 12.0% compared with 5.9% for the unexposed group (prevalence odds ratio 2.2, 95% CI 1.7-2.7). The combined analyses also identified a small but statistically significant increase in mitral regurgitation not previously identified by individual studies (exposed 3.5%, unexposed 1.8%, prevalence odds ratio 1.6, 95% CI 1.05-2.3). Among patients exposed for <90 days, a trend toward more regurgitation was not statistically significant by either combined Food and Drug Administration criteria (exposed 6.8%, unexposed 5.8%, prevalence odds ratio 1.4, 95% CI 0.8-2.4) or by individual valve. Conclusions These data indicate that fenfluramine-associated valvular regurgitation is less common than initially reported, but still present in 1 of 8 patients treated for >90 days. (Am Heart J 2002;144:1065-73.)     

Efficacy and safety of crataegus extract WS 1442 in comparison with placebo in patients with chronic stable New York Heart Association class-III heart failure

Objective The purpose of this study was to investigate whether long-term therapy with crataegus extract WS 1442 is efficacious as add-on therapy to preexisting diuretic treatment in patients with heart failure with a more advanced stage of the disease (New York Heart Association [NYHA] class III), whether effects are dose dependent, and whether the treatment is safe and well tolerated. Methods Exercise capacity was assessed by use of seated bicycle ergometry with incremental workloads. Scores for subjective symptoms and complaints made by the patients were analyzed. Efficacy and tolerability of the treatments were judged by both the patients and investigators. Safety was assessed by the documentation of adverse events and the safety laboratory. Results A total of 209 patients were randomized to treatment with 1800 mg of WS 1442, 900 mg of WS 1442, or with placebo. After 16 weeks of therapy with 1800 mg of WS 1442 per day, maximal tolerated workload during bicycle exercise showed a statistically significant increase in comparison with both placebo and 900 mg of WS 1442. Typical heart failure symptoms as rated by the patients were reduced to a greater extent by WS 1442 than by placebo. This difference was significant for both doses of WS 1442. Both efficacy and tolerability were rated best for the 1800 mg of WS 1442 group by patients and investigators alike. The incidence of adverse events was lowest in the 1800 mg of WS 1442 group, particularly with respect to dizziness and vertigo. Conclusions The data from this study confirm that there is a dose-dependent effect of WS 1442 on the exercise capacity of patients with heart failure and on typical heart failure-related clinical signs and symptoms. The drug was shown to be well tolerated and safe. (Am Heart J 2002;143:910-5.)     

The heart in neurofibromatosis type 1: an echocardiographic study

Background Comprehensive data are unavailable for cardiac abnormalities in patients with neurofibromatosis type 1 (NF1). The goal of this study was to evaluate the prevalence of cardiovascular abnormalities with echocardiography with color Doppler scan (ECHO) in a large, consecutive series of patients with NF1. Methods We studied 48 patients with NF1 (mean age, 10 years). Thirty healthy subjects comparable for age and sex served as the control group. All ECHO studies were performed by the same cardiologist and reviewed by a second cardiologist blinded to the physical findings of the subjects. Results Cardiac abnormalities were found in 13 of the 48 young patients (27%). A secundum atrial septal defect with a left to right shunt was found in 2 children. ECHO evidence of mild left pulmonary artery stenosis was found in 1 participant. A moderate coarctation of the thoracic aorta was found in 1 patient. ECHO criteria for mitral valve prolapse and evidence of trivial mitral regurgitation with myxomatous mitral valve was present in 1 case. Mild mitral regurgitation was found in 2 patients. A regurgitant mild flow signal was detected from the aortic valve in 2 subjects. Atrial septal aneurysm was found in 2 patients without patent foramen ovale. Two patients had septal to posterior left ventricular free wall ratio greater than 1.5, suggesting hypertrophic cardiomyopathy. Conclusion This is the first attempt to evaluate the prevalence of cardiovascular abnormalities in patients with NF1 with ECHO. The study's most striking finding is the high prevalence of cardiovascular abnormalities. Congenital lesions have potential long-term hemodynamic consequences that justify an early diagnosis. Thus, a cardiologic assessment at regular intervals, including ECHO study, is mandatory for patients with NF1. (Am Heart J 2002;143:883-8.)     

Use of an implantable loop recorder in the evaluation of children with congenital heart disease

Background A recently developed implantable loop recorder (ILR) has been used in adult patients whose syncope remains unexplained in spite of extensive investigations. Syncope in the patient with congenital heart disease presents a diagnostic challenge. We applied this technology to a cohort of pediatric patients. Methods We reviewed our experience with an ILR in patients with congenital heart disease with syncope or palpitations after conventional investigations failed to identify a cause for the symptoms. Results ILRs were implanted in 4 patients with congenital heart disease at 2 centers for investigation of syncope (n = 2), near-syncope (n = 1), and palpitations (n = 1). Implantations were performed at a mean age of 5.9 ± 0.9 years (4.2 to 7.6 years) and a mean weight of 26.7 ± 6.6 kg (15.7 to 42.5 kg) with patients under general anesthesia, with no complications. All patients experienced typical symptoms and activated the device appropriately at a median of 86 days (46 to 102) after implantation. Each patient had good-quality data that allowed interpretation of the rhythm. In 2 of 4 cases, a likely cause for the symptoms was identified, with exclusion of more malignant arrhythmic diagnoses in all patients. Escalation of therapy was avoidable in all patients on the basis of the data recorded by the ILR. Conclusions Recently developed loop recorder technology can be implanted in the young child without difficulty. The ILR proved to be very useful for excluding malignant arrhythmias as a cause of symptoms in these patients at high risk. (Am Heart J 2002;143:366-72)     

Whom Should I Refer in 2014 for Cardiac Resynchronization?

Heart failure continues to be a significant source of morbidity and mortality amongst Canadians. Many patients remain symptomatic despite guideline-directed medical therapy. For drug-refractory patients with dyssynchronous systolic heart failure, cardiac resynchronization therapy (CRT) has reliably reduced heart failure hospitalizations and related deaths. Unfortunately, despite significant advancements in technology and our understanding of its clinical effect, the CRT nonresponder rate remains approximately 30%. Great efforts have been invested into identifying clinical predictors of CRT response. Left bundle branch block conduction delay and wider QRS (> 150 ms) have consistently been associated with clinical response to CRT, earning them the strongest recommendations in the revised guidelines in Canada and across the world. Due in large part to the benefit observed in the Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (RAFT) trial, patients with mild heart failure symptoms (New York Heart Association class II) are now also candidates for resynchronization therapy. Patients with atrial fibrillation, non-left bundle branch block conduction patterns, and chronic right ventricular pacing have historically been associated with poor response. However, these populations remain grossly underrepresented in the large trials. In the absence of more data, these patients continue to receive weaker recommendations for CRT in the guidelines.     

Association of the human minK gene 38G allele with atrial fibrillation: evidence of possible genetic control on the pathogenesis of atrial fibrillation

Background Human minK protein is the β-subunit of I_Ks potassium channel and plays an important role in cardiac cellular electrophysiology. We investigated the association between human atrial fibrillation and the polymorphism of minK gene (38G or 38S) with a case-control study. Methods We included 108 patients with atrial fibrillation and 108 control subjects. The case patients and control subjects were matched regarding age, sex, presence of valvular heart disease, and presence of left ventricular dysfunction. The genotype of minK was determined with polymerase chain reaction and restriction fragment analysis. Results The results showed an association between the minK 38G allele and atrial fibrillation. The odds ratios for atrial fibrillation in patients with 1 and 2 minK 38G alleles were 2.16 (95% CI 0.81-5.74) and 3.58 (95% CI 1.38-9.27), respectively, when compared with patients without minK 38G allele. In a logistic regression model, the odds ratio for atrial fibrillation was 1.80 (95% CI 1.20-2.71, P < .0046) for patients with 1 more minK 38G allele. Conclusion We report the association between the minK 38G allele and clinical atrial fibrillation. Our findings suggest possible genetic control on the pathogenesis of atrial fibrillation. (Am Heart J 2002;144:485-90.)     

Outcome of significant functional tricuspid regurgitation after percutaneous mitral valvuloplasty

Background The outcome of significant functional tricuspid regurgitation (TR) associated with mitral stenosis (MS) after percutaneous mitral valvuloplasty (PMV) remains to be clarified. Methods From 265 patients who underwent PMV at our institution from 1995 to 2000 and who were regularly observed, we selected 71 patients (55 women, mean age 43 ± 11 years) who showed significant moderate to severe functional TR before PMV. We analyzed data from the echocardiograms performed before, 24 hours after, and long after the intervention (29 ± 12 months) and analyzed clinical outcomes. Resolution of TR was defined as trace or mild TR on the follow-up color Doppler study. Results Patients with moderate to severe TR showed more severe MS and pulmonary hypertension and more atrial fibrillation than patients with less than moderate TR. TR was resolved on the follow-up echocardiography in 23 of the 71 patients with significant TR before PMV (32%). The TR jet area before PMV (P < .05) and the late decrement of peak transmitral pressure gradient (P < .01) were independent determinants of resolution. TR was resolved in only 6.7% of patients (1/15) with an unsuccessful long-term PMV result, but was resolved in 39% of patients (22/56) with a successful long-term result (P < .05). During the clinical follow-up period (mean length 38 ± 20 months), 4 patients underwent open heart surgery 24 to 39 months after PMV, and there was no overall mortality. Conclusions Significant functional TR was associated with more severe MS, and it could be diminished when the transmitral pressure gradient was sufficiently relieved with PMV. (Am Heart J 2003;145:371-6.)     

Iodine-123 metaiodobenzylguanidine scintigraphic analysis of myocardial sympathetic innervation in patients with AL (primary) amyloidosis

Background Although a high incidence of myocardial adrenergic denervation has been reported in patients with familial amyloid polyneuropathy, assessment of cardiac sympathetic nerve function has not been available in patients with AL (primary) amyloidosis. Methods To test the hypothesis that myocardial sympathetic nerve innervation might be impaired and variable according to the presence or absence of clinical autonomic abnormalities and congestive heart failure in AL amyloidosis, we examined 25 patients by use of iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy. Results Ten of the 16 patients without autonomic symptoms and 5 of the 9 patients with autonomic neuropathy showed congestive heart failure. The heart/mediastinal activity (H/M) ratio (1.53 ± 0.06 vs 1.29 ± 0.05 at 3 hours, P < .001) and myocardial washout ratio (41.5% ± 4.8% vs 30.8% ± 4.0%, P < .001) of MIBG were significantly increased in patients without autonomic symptoms compared with patients showing autonomic neuropathy. In patient groups with and without autonomic dysfunction, patients demonstrating congestive heart failure exhibited a significantly decreased H/M ratio and increased washout compared with patients with no heart failure, and left ventricular fractional shortening was positively correlated with the H/M ratio and inversely correlated with the washout ratio. There were significant correlations between the low-frequency component of the heart rate variability and the H/M ratio and washout ratio in the entire patient population. Conclusions Patients with AL amyloidosis and no autonomic dysfunction showed variable degrees of enhanced cardiac adrenergic neuronal activity with presynaptic sympathetic dysfunction. In contrast, patients with AL amyloidosis and autonomic neuropathy exhibited prominent myocardial adrenergic denervation with normal or impaired sympathetic neural function of the heart. This study demonstrates that myocardial uptake and turnover of MIBG in patients with AL amyloidosis are heterogeneous and dependent on the presence or absence of congestive heart failure and cardiac autonomic dysfunction. (Am Heart J 2002;144:122-9.)     

Prognostic importance of systolic and diastolic function after acute myocardial infarction

Background Although risk stratification after acute myocardial infarction (AMI) often is focused on systolic left ventricular (LV) function, it appears that a more complete study of ventricular function including assessment of LV filling would be useful. Doppler echocardiography allows assessment of LV filling, and with the use of the Tei index (sum of isovolumic relaxation and contraction times divided by ejection time), a global estimate of ventricular function may be obtained. Therefore, the aim of this study was to determine the prognostic importance of LV systolic, diastolic, and overall LV function in a large consecutive population with AMI.Methods Echocardiography was performed within 6 days of AMI. LV systolic, diastolic, and global function was assessed by means of wall motion index (WMI), mitral flow pattern, and Tei index. The primary end point was all-cause death.Results Of 799 enrolled patients, 197 died during a median follow-up of 34 months. In a multivariate model including WMI and clinical parameters, WMI had important prognostic information. When mitral filling pattern and quartiles of Tei index were added to the model, restrictive filling (mitral deceleration time <140 ms) was associated with a risk ratio of 1.9 (95% CI 1.3-2.7, P < .0001, Tei index values of >0.68/0.56-0.68/0.46-0.55/<0.46 were associated with risks of 4.0 [2.1-6.9]/2.3 [1.5-3.9]/2.1 [1.2-3.6]/1.0, P < .001). In this model, WMI had no prognostic value (P = .18).Conclusions Mitral deceleration time and the Tei index have independent and important prognostic value after AMI. (Am Heart J 2003;145:147-153.)     

Prognostic significance of mitral regurgitation and tricuspid regurgitation in patients with left ventricular systolic dysfunction

Background Mitral regurgitation (MR) and tricuspid regurgitation (TR) frequently develop in patients with left ventricular systolic dysfunction (LVSD). Ventricular volume overload that occurs in patients with MR and TR may lead to progression of myocardial dysfunction. We hypothesized that MR and TR would provide markers of risk in patients with LVSD. Methods We reviewed clinical, electrocardiographic, and echocardiographic data on 1421 consecutive patients with LVSD (left ventricular ejection fraction ≤35%). Predictors of survival (freedom from death or United Network for Organ Sharing [UNOS]-1 transplantation) were identified in a multivariable analysis with a Cox proportional hazards analysis. The impact of MR and TR (none to mild, moderate, or severe) then was assessed separately with Kaplan-Meier survival analysis. Results During the follow-up period (mean ± SD, 365 ±364 days), death occurred in 435 study subjects (31%) and UNOS-1 transplantation in 28 subjects (2%). Multivariable predictors of poor outcome included increasing MR and TR grade, cancer, coronary artery disease, and absence of an implantable cardiac defibrillator. Relative risk was 1.84 (95% CI 1.43-2.38) for severe MR and 1.55 (95% CI 1.14-2.11) for severe TR. Survival with Kaplan-Meier analysis related inversely to MR grade (none to mild 1004 ±31 days, moderate 795 ±34 days, severe 628 ±47 days, P < .0001) and TR grade (none to mild 977 ±28 days, moderate 737 ±40 days, severe 658 ±55 days, P = .0001). Conclusion Patients with severe MR or TR represent high-risk subsets of patients with LVSD. Future study is warranted to determine whether pharmaceutical or surgical strategies to relieve MR and TR have a favorable impact on survival. (Am Heart J 2002;144:524-9.)