Heart-Rate Recovery Index Is Impaired in Beh?et's Disease

Behçet''s disease, a multisystemic inflammatory disorder, has been associated with a number of cardiovascular dysfunctions, including ventricular arrhythmias and sudden cardiac death. Heart-rate recovery after exercise can provide both an estimate of impaired parasympathetic tone and a prognosis in regard to all-cause and cardiovascular death. The aim of our study was to evaluate heart-rate recovery in Behçet''s diseaseFrom January through July 2008, we examined at our outpatient clinic and prospectively enrolled 30 consecutive patients with Behçet''s disease and 50 healthy control participants who were matched for age and sex. Basal electrocardiography, echocardiography, and treadmill exercise testing were performed in all patients and control participants. The heart-rate recovery index was calculated in the usual manner, by subtracting the 1st-minute (Rec1), 2nd-minute (Rec2), and 3rd-minute (Rec3) recovery heart rates from the maximal heart rate after exercise stress testing.Patients with Behçet''s disease exhibited significantly lower heart-rate recovery numbers, compared with healthy control participants: Rec1, 24.28 ± 8.2 vs 34.4 ± 7.6, P = 0.002; Rec2, 49.28 ± 11.2 vs 57.5 ± 7.0, P < 0.05; and Rec3, 56.2 ± 12.11 vs 67.4 ± 8.7, P = 0.014.To our knowledge, this is the 1st study that shows an impaired heart-rate recovery index (indicative of reduced parasympathetic activity) among patients with Behçet''s disease. Given the independent prognostic value of the heart-rate recovery index, our results may explain the increased occurrence of arrhythmias and sudden cardiac death in Behçet''s patients. Therefore, this index may be clinically useful in the identification of high-risk patients.Key words: Arrhythmias, cardiac; autonomic nervous system; Behcet syndrome/complications; electrocardiography; exercise test; exercise tolerance; heart rate; nervous system diseases; parasympathetic nervous system; predictive value of tests; prognosis; prospective studies; sympathetic nervous system; tachycardia, ventricular; vagus nerveHulusi Behçet first described Behçet''s disease in 1937 as a triad of relapsing uveitis and recurrent aphthous ulcers of the mouth and genitalia.¹ Prominent clinical manifestations include involvement of the mucocutaneous, ocular, gastrointestinal, respiratory, neurologic, urogenital, articular, and cardiovascular systems.^2,3 Cardiovascular system involvement mostly takes the form of endocarditis, myocarditis, pericarditis, intracardiac thrombosis, endomyocardial fibrosis, coronary arteritis, myocardial infarction, and valvular diseases.^4–12 Besides these manifestations, there have been reports^13–15 of an increased incidence of ventricular arrhythmias and sudden cardiac death—yet the mechanism of these events remains unclear. Involvement of the central nervous system is well known to occur in Behçet''s disease^16,17; peripheral nervous system involvement has also been reported (albeit rarely)¹⁸; and the autonomic nervous system (ANS) is often affected subclinically. However, previous studies^19–24 have revealed apparently contradictory findings, such as the occurrence, in association with Behçet''s disease, of both hypoactivity and hyperactivity in the sympathetic and parasympathetic systems.

Heart-Rate Recovery Index

The heart-rate recovery (HRR) index is calculated by subtracting the 1st-, 2nd-, and 3rd-minute recovery heart rates from the maximal heart rate after an exercise stress test (whether maximal or submaximal). The heart rate declines during the recovery period after a stress test, mainly during the early recovery period, due to parasympathetic activity.²⁵ Sympathetic activity increases during exercise and diminishes during recovery, so that previously suppressed parasympathetic activity becomes dominant during recovery and reduces the heart rate. This decline is blunted by decreased myocardial function and reduced exercise capacity. Several studies have shown that an abnormal HRR, defined as a failure of heart rate to decrease 12 beats or more during the 1st minute after peak exercise, independently predicts increased cardiovascular and all-cause mortality rates.^26–28 An abnormal HRR, as a reflection of decreased vagal reactivation, has been shown to be directly related to abnormal heart-rate variability and to insulin resistance.²⁹ Although one must keep in mind that HRR is not a precise test of sympathovagal balance (because numerous variables can cause HRR alterations), the impairment of HRR adds clinical information that might prove useful in the evaluation of Behçet''s patients for higher risk of serious arrhythmias. The aim of our study was to evaluate the HRR as a reflection of the function of the ANS in patients with Behçet''s disease.     

64-Slice Multidetector Computed Tomographic Evaluation of Arterial Conduit Patency after Off-Pump Coronary Artery Bypass Grafting

We set out to evaluate the accuracy of 64-slice multidetector row computed tomography (MDCT) in the evaluation of graft patency in 25 unselected patients who underwent off-pump revascularization with arterial conduits. A total of 73 coronary artery bypass grafts were examined by means of 64-slice MDCT. Postoperative clinical outcomes were also evaluated as indicators of early coronary bypass malfunction. Serial data from cardiac-specific biomarkers and from hemodynamic results were obtained in all patients. Two radiologists analyzed the MDCT images and reached consensus.No patients had evidence of postoperative acute myocardial infarction. Transient postoperative reduction of 5% to 8% in left ventricular ejection fraction was detected in 4 patients, independently of elevated biomarker serum levels. A total of 73 conduits were available for the analysis. Two grafts were judged not evaluable because of poor visualization due to irregular heartbeat. The image quality was excellent in all other scanned grafts and anastomoses.We conclude that 64-slice MDCT technology enables accurate and reliable visualization of coronary bypass grafts with arterial conduits. We believe that it can be performed in large populations of postoperative bypass patients as a realistic alternative to coronary angiography.Key words: Coronary angiography, graft occlusion, vascular/radiography, myocardial revascularization, tomography, spiral computed, vascular patencyCoronary artery bypass grafting (CABG) performed with cardiopulmonary bypass (CPB) and cardiac arrest provides good early and late graft patency. However, CPB is believed to be a major cause of postoperative morbidity, and the resurgence of interest in surgery without CPB (“off-pump”) reflects an attempt to avoid that additional morbidity.^1–3 The development of modern stabilizers and intracoronary shunts has made off-pump coronary surgery accessible and technically feasible. There is evidence that off-pump surgery, in comparison with on-pump surgery, may decrease the incidence of postoperative complications.^4–6 Although the extensive use of arterial conduits in off-pump revascularization has provided anecdotal evidence of better long-term graft patency and decreased need for reintervention, there is not sufficient evidence from randomized studies to support that contention.^7,8The postoperative assessment of bypass conduits and anastomosis after CABG is important in order to evaluate surgical results. Usually, CABG patency can be evaluated only indirectly, by intraoperative flow measurement. Until recently, selective bypass graft angiography has been considered the gold standard for the evaluation of early and late bypass patency, but it is invasive and carries risks of such serious complications as myocardial infarctions, embolic events, graft dissections, arrhythmias, and strokes.^9–11 Therefore, in the last 20 years, several trials have investigated the potential of computed tomography (CT) and magnetic resonance imaging as noninvasive alternatives for the visualization of CABG patency.¹² Although both methods have been limited by sensitivity to motion artifacts, recent advances in scanner performance—faster tube rotation and higher numbers of detector rows—have enabled thinner slices and better spatial resolution.^13–16 The 64-slice multidetector CT (MDCT) has indeed shown improved sensitivity and specificity for assessing graft patency.^14,17–20 The American Heart Association Committee, in a recent statement, has definitively validated the sensitivity (93%) and specificity (96%) of 64-slice MDCT for the detection of bypass stenoses or occlusions.²¹The aim of our prospective study was to investigate graft quality and patency in an unselected group of CABG patients who underwent noninvasive evaluation of their new arterial conduits by means of 64-slice MDCT.     

Posterobasal Left Ventricular Aneurysms: Surgical Treatment and Long-Term Outcomes

This retrospective study analyzes short- and long-term outcomes in 18 patients who underwent repair of posterobasal left ventricular aneurysm from January 1993 through December 2009. As concomitant procedures, mitral reconstruction was performed in 4 patients, ventricular septal defect repair in 2 patients, and coronary artery bypass grafting in 17 patients. In regard to surgical technique, 10 patients underwent patch repair and 8 underwent closure by linear suture.The in-hospital mortality rate was 11% (2 patients). An intra-aortic balloon pump was placed postoperatively in 1 patient. One patient underwent reoperation for mediastinitis and 2 for bleeding. The 1-, 5-, and 10-year survival rates were 82%, 76%, and 52%, respectively.Posterobasal left ventricular aneurysm repair can be performed with low short-term mortality rates and good long-term outcomes. It must be judged whether a linear repair or patch repair is better, in accordance with aneurysm size and the concomitant operative procedure, if any.Key words: Aneurysm, left ventricular; aneurysmectomy; cardiac surgical procedures/mortality; heart aneurysm/mortality/surgery; heart ventricle/surgery; myocardial infarction; retrospective studiesPosterior left ventricular (LV) aneurysms are less common than anterior aneurysms.^1–3 Their prevalence in large series has usually been reported as less than 10%.^2–4 The posterobasal part of the heart is supplied by the left circumflex coronary artery and by terminal branches of the right coronary artery.⁵ Pathologic states of these branches cause inferoposterior or posterolateral LV aneurysm.³ Posterior aneurysms can be accompanied by various degrees of mitral insufficiency⁶ and by ventricular septal defects (VSD).⁷ A 2004 study reported mitral insufficiency of grade 2/4 or higher in all 13 patients who underwent repair of aneurysm due to posterior myocardial infarction (MI).⁶ Our study investigates operative results among patients who underwent surgery for posterior LV aneurysm. Our surgical approach is discussed in terms of short- and long-term outcomes.     

Coronary Ostial Stenosis after Aortic Valve Replacement: Successful Treatment of 2 Patients with Drug-Eluting Stents

Coronary ostial stenosis is a rare but potentially serious sequela after aortic valve replacement. It occurs in the left main or right coronary artery after 1% to 5% of aortic valve replacement procedures. The clinical symptoms are usually severe and may appear from 1 to 6 months postoperatively. Although the typical treatment is coronary artery bypass grafting, patients have been successfully treated by means of percutaneous coronary intervention.Herein, we present the cases of 2 patients in whom coronary ostial stenosis developed after aortic valve replacement. In the 1st case, a 72-year-old man underwent aortic valve replacement and bypass grafting of the saphenous vein to the left anterior descending coronary artery. Six months later, he experienced a non-ST-segment-elevation myocardial infarction. Coronary angiography revealed a critical stenosis of the right coronary artery ostium. In the 2nd case, a 78-year-old woman underwent aortic valve replacement and grafting of the saphenous vein to an occluded right coronary artery. Four months later, she experienced unstable angina. Coronary angiography showed a critical left main coronary artery ostial stenosis and occlusion of the right coronary artery venous graft. In each patient, we performed percutaneous coronary intervention and deployed a drug-eluting stent. Both patients were asymptomatic on 6-to 12-month follow-up. We attribute the coronary ostial stenosis to the selective ostial administration of cardioplegic solution during surgery. We conclude that retrograde administration of cardioplegic solution through the coronary sinus may reduce the incidence of postoperative coronary ostial stenosis, and that stenting may be an efficient treatment option.Key words: Angioplasty, transluminal, percutaneous coronary; aortic valve/surgery; cardiac surgical procedures/adverse effects; coronary artery disease/etiology/prevention & control; coronary stenosis/diagnosis/etiology/therapy; heart valve prosthesis implantation/adverse effects; iatrogenic disease/prevention & control; perfusion/adverse effects/instrumentation; postoperative complications/therapy; treatment outcomeCoronary ostial stenosis is a rare but potentially serious postoperative sequela of aortic valve replacement (AVR). Ostial stenosis can occur in the left main coronary artery (LMCA) or in the right coronary artery (RCA). The condition, first described by Roberts and Morrow in 1967,¹ is believed to occur after 1% to 5% of AVR procedures.^2–7 No underlying cause has been determined. The clinical symptoms of coronary ostial stenosis are usually severe and can appear from 1 to 6 months postoperatively.^8,9 Although the typical treatment is coronary artery bypass grafting (CABG), patients have been successfully treated by means of percutaneous coronary intervention (PCI).^10–15 Herein, we present the cases of 2 patients in whom coronary ostial stenosis developed after AVR, discuss their PCI treatment, and offer our conclusion regarding the feasibility of PCI in the treatment of coronary ostial stenosis.     

Coronary Artery Diameter Related to Calcium Scores and Coronary Risk Factors as Measured with Multidetector Computed Tomography: A Substudy of the Accuracy Trial

Arterial remodeling, an early change of atherosclerosis, can cause dilated arterial diameter. We measured coronary artery diameter with use of noncontrast 64-slice multidetector computed tomography (MDCT), and studied its association with coronary artery calcium levels and traditional coronary risk factors.We included 140 patients from the ACCURACY trial whose noncontrast MDCT images showed measurable coronary arteries. Using 3 measurements of left main coronary artery (LMCA) and right coronary artery (RCA) diameters within 3 mm of the ostium, we associated the results with traditional coronary risk factors and calcium scores.The prevalence of LMCA and RCA calcium was 22% and 51%, respectively. Mean arterial diameters were 5.67 ± 1.18 mm (LMCA) and 4.66 ± 1.08 mm (RCA). Correlations for LMCA and RCA diameters in 50 randomly chosen patients were 0.91 and 0.93 (interobserver) and 0.98 and 0.93 (intraobserver). Adjusted odds ratios for the relationship of LMCA and RCA diameters to calcium in male versus female patients were 5.65 (95% confidence interval [CI], 2.78–11.5) and 4.35 (95% CI, 2.24–8.47), respectively. Adjusted ratios and 95% CIs for the association of larger RCA diameter with age, hypertension, and body mass index were 1.36 (1.00–1.86), 3.13 (1.26–7.78), and 1.60 (1.16–2.22), respectively.Arterial diameters were larger in women and patients with higher calcium levels, and body mass index and hypertension were predictors of larger RCA diameters. These findings suggest a link between arterial remodeling and the severity of atherosclerosis.Key words: Arteriosclerosis/complications/pathology, calcinosis/complications, coronary artery disease/etiology/pathology, coronary vessels/pathology/physiology, dilatation, pathologic/pathology, disease progression, models, cardiovascular, regression analysis, risk assessment, tomography, x-ray computed/methodsAn early change of atherosclerosis is arterial remodeling, which can result in dilated arterial diameter. In positive (expansive) arterial remodeling, luminal size is often preserved.^1–4 Conventional coronary angiography and myocardial perfusion imaging detect anatomically significant and hemodynamically relevant luminal stenosis, respectively, but perform less well in depicting atherosclerotic disease in its earlier stages when luminal integrity has not yet been compromised by positive vascular remodeling. Imaging studies of early culprit lesions in patients with acute coronary syndrome have revealed an association of echolucent plaque and positive remodeling with unstable clinical presentation.^5–7 Many studies of normal human coronary artery size have been conducted during postmortem examinations of the heart.^8–17 Investigators using intravascular ultrasonography, cardiac magnetic resonance, and cardiovascular computed tomography (CT) have suggested that coronary plaque rupture could occur in positively remodeled lesions.^18,19 Large positively remodeled lesions as predictors of plaque rupture are the subject of active research. Intravascular ultrasonography yields good views of coronary artery lumina and arterial walls and can help to reveal disease that is not angiographically evident; however, it is an invasive technique that is unsuitable as a screening procedure.^20–22 Coronary artery calcium (CAC), as evaluated by means of cardiovascular CT, is currently used as a surrogate marker of atherosclerosis.^23,24 In this study, we used noncontrast 64-slice multidetector computed tomography (MDCT) to measure coronary artery diameters in patients who had been referred for CAC scoring. We then used these measurements to study the relationship of increased coronary artery diameter to CAC and to traditional cardiovascular (CV) risk factors.     

Low Serum Triglyceride Levels as Predictors of Cardiac Death in Heart Failure Patients

Understanding the influence of sex differences on predictors of cardiac mortality rates in chronic heart failure might enable us to lengthen lifetimes and to improve lives. This study describes the influence of sex on cardiovascular mortality rates among chronic heart failure patients.From January 2003 through December 2009, we evaluated 637 consecutive patients (409 men and 228 women) with chronic heart failure, who ranged in age from 18 through 94 years (mean age, 64 ± 13 yr) and ranged in New York Heart Association (NYHA) functional class from II through IV. The mean follow-up period was 38 ± 15 months, the mean age was 64 ± 13 years, and the mean left ventricular ejection fraction was 0.27 ±0.11.By the end of the study, both sexes had similar cardiovascular mortality rates (36% men vs 37% women, P=0.559). In Cox regression analysis, NYHA functional class, triglyceride level, and history of coronary artery disease were independent predictors of cardiovascular death for women with chronic heart failure. For men with chronic heart failure, the patient''s age, ejection fraction, and sodium level were independent predictors of cardiovascular death.In a modern tertiary referral heart failure clinic, decreased triglyceride levels were, upon univariate analysis, predictors of poor outcomes for both men and women. However, upon Cox regression analysis, reduced triglyceride levels were independent predictors of cardiac death only in women.Key words: Cachexia/blood, chronic disease, heart failure/mortality, female, follow-up studies, male, predictive value of tests, prognosis, risk assessment, sex factors, survival analysis, triglycerides/blood, univariate analysisThe 5-year survival rate for chronic heart failure (CHF) remains at 50%, with mortality rates higher for men than for women (relative risk=1.33, P < 0.001). After diagnosis with heart failure, women tend to have a better prognosis and to survive longer than men.¹ Given the greater life expectancy of women in the developed world, the overall impact of heart failure is still very important for them.² Although the CHF death rate seems to be lower or the same in women, most available scientific evidence regarding the influence of male versus female sex on the prognosis of CHF patients derives from observational studies and retrospective analyses, and women are known to be underrepresented in clinical trials.³ These studies report divergent findings concerning the prognosis of CHF patients according to sex, mainly attributable to the study characteristics, the cause of the heart failure, and the type of population studied.^2,4–6 Few reports deal with the differences between men and women in specialized heart failure clinics or units.Chronic heart failure can lead to a catabolic state and eventually to cachexia in advanced cases. There is preferential loss of fat but also a decline in lean body mass. Reduced efficiency of adenosine triphosphate production by mitochondria, reduced appetite, malabsorption, and reduced levels of anabolic steroids might play a role.⁷ Patients with advanced heart failure have severe symptoms, a high mortality rate, and a low cholesterol level.⁸ This can be due to inflammation, endotoxins, adrenergic activation, oxidative stress, tissue injury, and cachexia.^9,10 Liver-function abnormalities are most commonly seen in patients with low cardiac indices and resolve with compensation of heart failure; they are not associated with clinically apparent hepatic disease.¹¹ It has been determined that liver dysfunction is frequent in CHF and is characterized by a predominantly cholestatic enzyme profile that worsens with disease severity.¹² Functional liver mass was significantly decreased in New York Heart Association (NYHA) functional class IV patients, in comparison with NYHA II and III patients and with subjects in a control group. The functional liver mass in patients with systolic CHF did not show any correlations with left ventricular ejection fraction (LVEF), but it did correlate strongly with left atrial diameter.¹³ Dysfunction of the liver during heart failure syndrome can be another explanation of decreased cholesterol level in CHF.Triglycerides are neutral lipids consisting of a glycerol backbone and 3 long-chain fatty acids. These molecules are a major source of stored energy in such diverse tissues as adipose tissue and skeletal muscle, and they are integral components of lipoprotein particles synthesized by the liver and small intestine.¹⁴ In advanced heart failure, mechanisms similar to those that cause low cholesterol levels might cause low triglyceride levels. It seems that heart failure might alter both the production and the storage of triglycerides. Loss of a major energy source can adversely affect the survival of patients with CHF. The aim of this study was to determine the prognostic significance of triglyceride levels for both men and women who have CHF.     

Quadricuspid Aortic Valve without Severe Dysfunction despite Advanced Age

We report the case of a 75-year-old woman who presented with stable angina and with a quadricuspid aortic valve, which consisted of 4 equal-sized leaflets that were diagnosed incidentally upon coronary angiography. Despite the patient''s advanced age, the abnormal valve was functioning almost normally.Key words: Aged, aortic valve/anomalies, coronary angiography, heart defects, congenital/diagnosis, heart valve diseasesSince the 1st case of quadricuspid aortic valve was published in 1969,¹ the total number of reported cases has reached approximately 200.² The diagnosis—more frequent in men—is commonly made between the 5th and 6th decades of life.^1,2 If valve replacement is needed (due mostly to severe aortic insufficiency), that too occurs most often in the 5th or 6th decade.³ However, we report a case in which a woman''s quadricuspid aortic valve was diagnosed in her 8th decade and did not result in significant valvular dysfunction, despite her advanced age.     

Non-Gadolinium-Enhanced 3-Dimensional Magnetic Resonance Angiography for the Evaluation of Thoracic Aortic Disease: A Preliminary Experience

We compared image quality and diagnostic accuracy of a noncontrast 3-dimensional magnetic resonance angiography (NC-MRA) technique (balanced steady-state free-precession sequence) to contrast-enhanced MRA (CE-MRA) for evaluation of thoracic aortic disease.The CE-MRA provides 3-dimensional high-resolution images of the thoracic aorta that are important in the evaluation of patients with aortic disease. However, recent concerns with the potential nephrotoxic effects of gadolinium contrast medium limit the application of CE-MRA for patients who have significant renal insufficiency.Twenty-one patients (mean age, 51 yr; 18 men) who underwent NC-MRA and CE-MRA for evaluation of thoracic aortic disease were retrospectively identified. Data sets were reviewed by 2 readers who were blinded to the patients'' information. The thoracic aorta was divided into 5 segments. Image quality and reader confidence for diagnosis of aortic pathology were rated on 5-point scales. The Wilcoxon matched-pairs signed rank test and the Student t test were used for comparisons.The NC-MRA identified all pathologic findings with 100% diagnostic accuracy and similar reader confidence, when compared with CE-MRA. Although overall image quality was not significantly different, superior image quality was observed at the aortic root (4.4 ± 0.8 vs 3.2 ± 0.9, P <0.0005) and ascending aorta (4.1 ± 1 vs 3.7 ± 0.9, P=0.05) respectively.In conclusion, NC-MRA is a useful alternative for evaluation and follow-up of thoracic aortic disease, especially for patients with poor intravenous access or contraindications to gadolinium use.Key words: Aneurysm, dissecting/diagnosis; aorta, thoracic/pathology; aortic aneurysm, thoracic/diagnosis; aortic diseases/diagnosis/radiography; artifacts; contrast media/toxici-ty; gadolinium/diagnostic use/toxicity; magnetic resonance angiography; retrospective studiesContrast-enhanced magnetic resonance angiography (CE-MRA) is often used for initial assessment and follow-up of thoracic aortic disease.^1,2 Fast, reproducible, 3-dimensional (3-D) high-resolution imaging of the thoracic aorta is essential for surgical planning and follow-up after intervention. Although computed tomographic angiography has advanced rapidly over the past few years and now can provide high-resolution images of the thoracic aorta, it has several drawbacks, including its use of ionizing radiation and nephrotoxic iodinated contrast agents and its inability to quantify blood flow. Contrast-enhanced MRA has such limitations as its need for intravenous gadolinium-chelate contrast, its frequent application without cardiac gating (which leads to motion artifacts), and its predominantly intraluminal imaging of the aorta³ (with restricted imaging of the aortic wall for the evaluation of mural and extraluminal disease such as intramural hematoma or vasculitis). Gadolinium--chelate contrast agents are far less likely to elicit allergic-type reactions than are iodinated contrast agents, and are, in general, considered safer for use in patients with impaired renal function. Recently, however, they have been associated with nephrogenic systemic fibrosis, a potentially life-threatening disease that chiefly affects patients on dialysis or with severe renal dysfunction.^4,5Electrocardiographic (ECG) gated 2-dimensional noncontrast imaging techniques, including spin-echo, gradient-echo, and time-of-flight pulse sequences, enable improved visualization of the aorta without need for contrast but are hampered by long-er imaging times and nonvolumetric data acquisition.⁶ Recently, a respiratory- and cardiac-gated, fat-suppressed, noncontrast 3-D magnetic resonance angiography (NC-MRA) technique (balanced steady-state free-precession sequence) has been developed for whole-heart imaging,^7,8 and this provides high and isotropic spatial resolution for the evaluation of coronary arteries.^9,10 It is unknown whether this technique can be applied to the imaging of various aortic diseases with reliable diagnostic accuracy, although recent preliminary results are promising.^11–13 The aim of this study was to examine our institution''s initial experience in comparing the image quality and diagnostic accuracy of NC-MRA to those of CE-MRA for the evaluation of the anatomy and pathology of the thoracic aorta and branch vessels.     

Relationship of Electro-mechanical Remodeling to Survival Rates after Cardiac Resynchronization Therapy

Cardiac resynchronization therapy, when added to optimal medical therapy, increases longevity in symptomatic congestive heart failure patients with left ventricular ejection fractions (LVEF) ≤0.35 and QRS durations >120 ms. Cardiac resynchronization therapy is also associated with electrical and mechanical reverse remodeling. We examined whether reverse remodeling predicts increased survival rates in non-trial settings.Recipients of cardiac resynchronization therapy and defibrillators (n=112; 78 men; mean age, 69 ± 11 yr) underwent repeat echocardiography and electrocardiography at least 90 days after device implantation. Forty patients had mechanical responses of at least 0.05 improvement in absolute LVEF; 56 had electrical responses (any narrowing of biventricular-paced QRS duration compared with the electrocardiogram immediately after therapy). During a mean follow-up period of 3.1 ± 1.7 years, 55 patients died. The average death rate per 100 person-years was lower among mechanical responders than nonresponders (9.2% vs 23.9%; P=0.009); the unadjusted hazard ratio was 0.39 (95% confidence interval [CI], 0.19–0.79).In a multivariate model adjusted for age, sex, baseline LVEF, and QRS duration, mechanical responders had 60% better survival than nonresponders (hazard ratio=0.40; 95% CI, 0.21–0.79; P=0.008). No difference in survival was observed in electrical response. In our association of absolute change in LVEF over the observed range with death (using restricted cubic splines), we observed a linear relationship with survival.In patients given cardiac resynchronization therapy, mechanical but not electrical remodeling was associated with better survival rates, suggesting that mechanical remodeling underlies this therapy''s mechanism of conferring a survival benefit.Key words: Cardiac resynchronization therapy/methods, combined modality therapy, heart conduction system/physiopathology, heart failure/mortality/physiopathology/therapy, predictive value of tests, survival analysis, ventricular dysfunction, left/mortality/prevention & control/therapy, ventricular remodelingIn selected heart-failure patients, cardiac resynchronization therapy (CRT) improves exercise tolerance, maximal oxygen consumption, and quality of life, and reduces the risks of repeat hospitalization for heart failure or death.^1,2 Lower left ventricular ejection fraction (LVEF) is a predictor of cardiac events independently of QRS duration or electrical evidence of dyssynchrony.^3,4 Secondary data analyses from clinical trials yielded better clinical outcomes in the context of reverse mechanical remodeling.^5,6 In addition, electrical dyssynchrony—commonly observed in patients with left ventricular (LV) dysfunction⁷—is a predictor of LV systolic dysfunction.^8,9 Data from clinical practice are sparse in regard to associations of reverse mechanical and electrical remodeling with improved survival rates. In this study, we examined the association between electromechanical reverse remodeling and survival rates in a tertiary-care hospital.     

Coronary Revascularization Alone or with Mitral Valve Repair: Outcomes in Patients with Moderate Ischemic Mitral Regurgitation

We sought to evaluate retrospectively the outcomes of patients at our hospital who had moderate ischemic mitral regurgitation and who underwent coronary artery bypass grafting (CABG) alone or with concomitant mitral valve repair (CABG+MVr).A total of 83 patients had a reduced left ventricular ejection fraction and moderate mitral regurgitation: 28 patients underwent CABG+MVr, and 55 underwent CABG alone. Changes in mitral regurgitation, functional class, and left ventricular ejection fraction were compared in both groups.The mean follow-up was 5.1 ± 3.6 years (range, 0.1–15.1 yr). Reduction of 2 mitral-regurgitation grades was found in 85% of CABG+MVr patients versus 14% of CABG-only patients (P < 0.0001) at 1 year, and in 56% versus 14% at 5 years, respectively (P = 0.1), as well as improvements in left ventricular ejection fraction and functional class. One- and 5-year survival rates were similar in the CABG+MVr and CABG-only groups: 96% ± 3% versus 96% ± 4%, and 87% ± 5% versus 81% ± 8%, respectively (P = NS). Propensity analysis showed similar results. Recurrent (3+ or 4+) mitral regurgitation was found in 22% and 47% at late follow-up, respectively.In patients with moderate ischemic mitral regurgitation, either surgical approach led to an improvement in functional class. Early and intermediate-term mortality rates were low with either CABG or CABG+MVr. However, an increased rate of late recurrent mitral regurgitation in the CABG+MVr group was observed.Key words: Cardiac surgical procedures, coronary artery bypass, coronary disease/complications/surgery, disease-free survival/trends, matched-pair analysis, mitral valve insufficiency/physiopathology/surgery, multivariate analysis, myocardial ischemia/complications/surgery, myocardial revascularization/methods/statistics & numerical data, postoperative period, recurrence, risk assessmentCoronary artery disease (CAD) can lead to ischemic mitral regurgitation (MR) due to myocardial ischemia or infarction in the absence of any intrinsic organic disease of the mitral valve. Uncorrected chronic MR is associated with a poor prognosis in patients after coronary revascularization by means of coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty.^1–5 Many investigators have evaluated the pathogenesis of ischemic MR and have been able to show the crucial role of changes in the geometry of the left ventricle (LV) and papillary muscle due to the myocardial scarring that results in annular dilation and leaflet tethering.^6–8 Because of higher morbidity and operative mortality rates associated with combined revascularization and mitral valve surgery,^3,4,9,10 some surgeons have advocated revascularization alone,^11,12 while others have recommended concomitant mitral valve surgery^{3,4,9,10,13–15} in order to optimize patients'' cardiac function and long-term prognosis.The clinical usefulness of combined surgery remains unclear due to the prolongation of cardiopulmonary bypass time and the additional technical complexity of such surgery in these patients. Although most surgeons would agree that mild MR can be treated by CABG alone and that severe MR should be corrected at the time of CABG, the optimal approach toward the management of moderate ischemic MR remains controversial. It has been shown that patients with moderate MR have lower survival rates after undergoing CABG alone than do patients who have no MR or mild MR,¹⁶ and that CABG alone leaves many patients with substantial residual MR.¹³ Although many studies have been undertaken in order to define the risk factors for high mortality rates and the appropriate approach, there is no clear consensus regarding the optimal treatment of these high-risk patients.Most published studies that have focused on differences in outcomes between CABG alone and with concomitant mitral valve repair (MVr) were not limited to a single MR grade, and various mitral valve surgical procedures were used. In this study, we reviewed the outcomes of the most problematic subgroup of patients in terms of surgical approach—patients with moderate MR. We evaluated the effectiveness of CABG alone and CABG with MVr with regard to changes in functional class, postoperative MR, LV function, and survival.     

Pathophysiology of the Syndrome: Biventricular Takotsubo Cardiomyopathy: Case Study and Review of Literature

Biventricular takotsubo cardiomyopathy is associated with more hemodynamic instability than is isolated left ventricular takotsubo cardiomyopathy; medical management is more invasive and the course of hospitalization is longer.In March 2011, a 62-year-old woman presented at our emergency department with abdominal pain, nausea, and vomiting. On hospital day 2, she experienced chest pain. An electrocardiogram and cardiac enzyme levels suggested an acute myocardial infarction. She underwent cardiac angiography and was found to have severe left ventricular systolic dysfunction involving the mid and apical segments, which resulted in a left ventricular ejection fraction of 0.10 to 0.15 in the absence of obstructive coronary artery disease. Her hospital course was complicated by cardiogenic shock that required hemodynamic support with an intra-aortic balloon pump and dobutamine. A transthoracic echocardiogram revealed akinesis of the mid-to-distal segments of the left ventricle and mid-to-apical dyskinesis of the right ventricular free wall characteristic of biventricular takotsubo cardiomyopathy. After several days of medical management, the patient was discharged from the hospital in stable condition.To the best of our knowledge, this is the first review of the literature on biventricular takotsubo cardiomyopathy that compares its hemodynamic instability and medical management requirements with those of isolated left ventricular takotsubo cardiomyopathy. Herein, we discuss the case of our patient, review the pertinent medical literature, and convey the prevalence and importance of right ventricular involvement in patients with takotsubo cardiomyopathy.Key words: Cardiomyopathies/radiography, hemodynamic instability/takotsubo, magnetic resonance angiography, takotsubo cardiomyopathy, biventricular/diagnosis, transient apical ballooning syndrome, ventricular dysfunction, left, ventricular dysfunction, rightTransient left ventricular apical ballooning syndrome (TLVABS) is an acute cardiac syndrome that typically is characterized by transient left ventricular (LV) wall-motion abnormalities, electrocardiographic (ECG) findings of ST-T segment changes, and minimal release of cardiac enzymes in the absence of significant stenosis of the coronary arteries (<50% luminal stenosis).^1–8 This syndrome was first described in Japan in 1991 and named takotsubo-like LV dysfunction in reference to the asynergy, which consists of hypokinesis or akinesis of the mid-to-apical LV and hyperkinesis of the basal LV extending over more than one coronary artery region.^8–11 Since then, this asynergy has been called takotsubo cardiomyopathy (TC), stress cardiomyopathy, ampulla syndrome, broken-heart syndrome, and neurogenic stunned myocardium.^12–14 Takotsubo cardiomyopathy presents clinically with chest pain and dyspnea associated with ECG changes, thereby mimicking ST-segment elevation myocardial infarction that is often preceded by emotional or physical stress.^1-7,9,10 Indeed ST-segment elevation is the most common ECG abnormality, reported in approximately 82% of patients with TC, followed by T-wave inversion in 64%.^8,15 This peculiar cardiac syndrome results in severe impairment of systolic function.There are several variants of TC. Isolated LV involvement is the most common variant, but right ventricular (RV) involvement is gaining increased recognition. Although there is only one documented case of isolated RV stress cardiomyopathy,¹⁶ the recognition of biventricular TC is increasing. It has been reported that RV involvement affects approximately 25% to 42% of patients diagnosed with TC.^12,13,17,18 In addition to isolated LV, isolated RV, and biventricular involvement, a variety of ballooning patterns has been observed. The typical apical-ballooning shape, with akinesis of the apical and mid-ventricular LV segments, is the most common; however, a mid-ventricular variant with apical sparing and a variant with isolated basal ballooning have been recognized.¹⁸ Left ventricular systolic dysfunction and heart failure—with simultaneous RV dysfunction—identifies a patient population with an extremely poor prognosis.¹⁹ Therefore, it is not surprising that TC with RV involvement appears to be associated with more severe LV dysfunction that results in significantly longer hospitalization and hemodynamic instability that is associated with a worse prognosis.^1-4,13,18 Clinicians need to be aware of the prevalence and complications of RV involvement and dysfunction, because it can affect patient management, morbidity, and, ultimately, mortality rates in substantial ways.The data concerning RV involvement in TC are sparse, because they are derived from several case reports and case series studies. This review of the literature documents the prevalence, pathophysiology, diagnostic imaging characteristics, clinical findings, management, and prognosis of patients with biventricular TC. Throughout this article, TC with RV involvement will be referred to as biventricular TC, whereas classic left ventricular TC (with apical ballooning) will be referred to as TLVABS. All of the documented cases of biventricular TC have been evaluated and analyzed in regard to how the patient presented, how the TC was diagnosed and managed, and how we can improve in managing the even more hemodynamically unstable biventricular TC, in comparison with TLVABS.     

Myocardial Perfusion Imaging and Cardiovascular Outcomes in a Cancer Population

Myocardial perfusion imaging can predict outcomes in cardiac patients. However, limited data exist regarding its prediction of cardiovascular outcomes in cancer patients. We sought to determine whether myocardial perfusion imaging predicts long-term cardiovascular outcomes in cancer patients.We performed a retrospective review of 787 consecutive patients at our institution who underwent myocardial perfusion imaging from January 2001 through March 2003. The Cox proportional hazard model was applied, and total cardiac events, cardiac death, and all-cause death were determined for 3 years. We considered P <0.05 to be statistically significant.Patients with abnormal myocardial perfusion imaging results were more likely to be male and older, with heart disease, more vascular risk factors, and lower left ventricular ejection fraction (0.52 ± 0.14 vs 0.63 ± 0.11; P <0.001) than patients with normal myocardial perfusion imaging results. Multivariate predictors of total cardiac events included age (P = 0.023), hyperlipidemia (P = 0.0021), pharmacologic myocardial perfusion imaging (P <0.01), left ventricular ejection fraction (P <0.001), and abnormal myocardial perfusion imaging (P = 0.012). Multivariate predictors of cardiac death included age (P = 0.026) and left ventricular ejection fraction (P = 0.0001). Multivariate predictors of all-cause death were age (P = 0.0001), atrial fibrillation (P = 0.0012), and smoking (P <0.001). Overall survival was improved when patients took aspirin (P = 0.0002) and upon each unit increase in left ventricular ejection fraction (P <0.001).Myocardial perfusion imaging in cancer patients can predict 3-year cardiac outcomes. Increasing age, atrial fibrillation, and smoking were associated with worse outcomes, whereas higher left ventricular ejection fraction and the taking of aspirin were protective.Key words: Aspirin/therapeutic use, comorbidity, coronary disease/epidemiology/radionuclide imaging, death, sudden, cardiac/prevention & control, electrocardiography, exercise test/methods/statistics & numerical data, heart/radionuclide imaging, multivariate analysis, neoplasms/epidemiology/mortality, predictive value of tests, proportional hazards model, retrospective studies, risk assessment/methods, ventricular function, leftThe use of myocardial perfusion imaging (MPI) for estimating cardiac risk and for guiding the management of heart disease has been validated in multiple studies.^1–6 Most of these studies were of patients with known or suspected coronary artery disease (CAD),^1–3,7 but without substantial comorbidities, such as cancer. Some authors have evaluated the role of other comorbidities, such as diabetes mellitus⁶ and advanced age,^4,5 in conjunction with CAD, and MPI is useful for risk stratification in these patients. However, there exists little information on the usefulness of MPI in cancer patients with coexistent CAD.⁷ This is a relevant concern, primarily due to substantially increased survival of patients with all types of cancer over the past 2 decades,⁸ which has resulted in cancer''s being thought of as a chronic disease. One of the most important factors that has been identified to predict outcomes in cancer patients is comorbidity, such as heart disease.⁹ The management of cardiac disease in cancer patients is emerging as a crucial approach for the improvement of outcomes. A 1999 study of more than 34,000 newly diagnosed cancer patients found that the prevalence of cardiovascular disease and hypertension was as high as 30% in patients who were older than 75 years and who had certain forms of cancer.¹⁰ Cardiovascular disease and cancer are the 2 leading causes of death worldwide, accounting for more than 70% of deaths.¹¹ In addition, cancer occurs as a comorbidity in cardiac patients more often than may be acknowledged. In fact, a recent community heart-failure study indicated that existing cancer occurred nearly as often as did peripheral arterial disease in a population of patients who had heart disease.¹² There is no doubt that cancer would have an important influence on morbidity and death in any population, especially in patients who have heart disease. Furthermore, the interaction between these 2 major diseases is currently unknown, because clinical trials involving cardiovascular disease generally exclude patients who have cancer, and, similarly, cancer-treatment trials exclude patients who have heart disease.We sought to define the outcomes of cancer patients who underwent MPI, in an effort to understand the clinical importance of such findings. To date, there are few data surrounding the performance of MPI in cancer patients, and previous studies have been limited to preoperative evaluations with short-term follow-up of 30 days.^7,13 We therefore analyzed the role of MPI in predicting 3-year outcomes in cancer patients.     

Atypical Transient Stress-Induced Cardiomyopathies with an Inverted Takotsubo Pattern in Sepsis and in the Postpartal State

Several cases of inverted Takotsubo cardiomyopathy—a variant form with hyperdynamic left ventricular apex and akinesia of the left ventricular base and mid-portion—have been reported recently, especially in association with cerebrovascular accidents and catecholamine cardiomyopathies. Herein, we describe 2 cases of inverted Takotsubo cardiomyopathy: one that occurred in a middle-aged woman who had a septic condition, and another in a young woman who was in the postpartal state. Such cases have not been reported previously.Key words: Cardiomyopathies/physiopathology/therapy/ultrasonography, coronary angiography, echocardiography, heart ventricles/physiopathology/radiography, postpartum period, sepsis, ventricular dysfunction/diagnosis/physiopathology, ventricular dysfunction, leftStress-induced cardiomyopathy is characterized by a transient abnormality of left ventricular (LV) apical wall motion, electrocardiographic changes, and minimal cardiac enzyme release. The condition mimics acute coronary syndrome in patients who have no angiographic stenosis upon coronary angiography. Recently, atypical stress-induced cardiomyopathies without involvement of the LV apex have been reported.¹ Most of the cases were transient midventricular ballooning syndrome with midventricular akinesia and normal wall motion of the LV base and apex,^1–3 and some were the “inverted Takotsubo pattern” cardiomyopathy that is characterized by a hyperdynamic LV apex and akinesia of the LV base and mid-portion.^4–6 Here, we describe 2 cases of inverted Takotsubo cardiomyopathy, one of which occurred in a middle-aged woman with a septic condition and one in a young woman who was in the postpartal state.     

Impact of C-Reactive Protein on In-Stent Restenosis: A Meta-Analysis

We sought to evaluate the impact of C-reactive protein (CRP) levels on in-stent restenosis after percutaneous coronary intervention.The plasma level of CRP is considered a risk predictor for cardiovascular diseases. However, the relationship between CRP and in-stent restenosis has been a matter of controversy. Meta-analysis reduces variability and better evaluates the correlation.We performed a systemic search for literature published in March 2008 and earlier, using MEDLINE®, the Cochrane clinical trials database, and EMBASE®. We also scanned relevant reference lists and hand-searched all review articles or abstracts from conference reports on this topic. Of the 245 studies that we initially searched, we chose 9 prospective observational studies (1,062 patients).Overall, CRP concentration was higher in patients who experienced in-stent restenosis. The weighted mean difference in CRP levels between the patients with in-stent restenosis and those without was 1.67, and the Z-score for overall effect was 2.12 (P=0.03). Our subgroup analysis that compared patients with stable and unstable angina showed a weighted mean difference in the CRP levels of 2.22 between the patients with and without in-stent restenosis, and the Z-score for overall effect was 2.23 (P=0.03) in 5 studies of unstable-angina patients. There was no significance in 4 studies of stable-angina patients.In spite of significant heterogeneity across the studies, our meta-analysis suggests that preprocedurally elevated levels of CRP are associated with greater in-stent restenosis after stenting and that this impact appears more prominent in unstable-angina patients.Key words: Angina pectoris/epidemiology, angioplasty, transluminal, percutaneous coronary, biological markers/blood, clinical trials as topic, coronary artery disease/etiology/physiopathology, coronary restenosis/etiology/pathology/prevention & control, C-reactive protein/analysis/metabolism, inflammation/complications, risk factors, stents/adverse effectsCoronary artery diseases remain the major cause of death in the Western world. Inflammation plays an important role in atherosclerotic disorders.^1–3 Modest elevation of plasma inflammatory markers, such as C-reactive protein (CRP), is considered a risk predictor for cardiovascular disease and is thought to reflect inflammation in atherosclerosis.^4,5The development of coronary stents has revolutionized the field of interventional cardiology by reducing the incidence of restenosis after balloon angioplasty.⁶ Intracoronary stents improve procedural success rates and increase the safety and effectiveness of procedures by decreasing the number of cardiovascular events. However, coronary stenting is still associated with a serious complication—in-stent restenosis (ISR).⁷Systemic inflammation characterizes the response to vascular injury after percutaneous coronary intervention (PCI).^8–10 Stent implantation, in particular, precipitates arterial intimal cellular proliferation and extracellular matrix synthesis that is mediated largely by inflammatory processes.¹¹ However, controversy exists regarding the clinical impact of early inflammatory response on ISR after coronary stent implantation. Previous studies have suggested that the magnitude of the systemic inflammation is linked to adverse late clinical outcomes after PCI.^12–14 In contrast, other studies have shown that levels of inflammatory markers after PCI appear similar and that reduction in restenosis after stenting is likely not mediated by the attenuation of systemic markers, such as CRP.^15,16 In view of these conflicting reports, we conducted a systematic review of evidence from observational studies, in order to evaluate the association between CRP levels and ISR rates after successful coronary stent implantation in patients with stable angina and unstable angina.     

Incidence and Outcomes of Contrast-Induced AKI Following Computed Tomography

Background and objectives: Most studies of contrast-induced acute kidney injury (CIAKI) have focused on patients undergoing angiographic procedures. The incidence and outcomes of CIAKI in patients undergoing nonemergent, contrast-enhanced computed tomography in the inpatient and outpatient setting were assessed.Design, setting, participants, & measurements: Patients with estimated glomerular filtration rates (GFRs) <60 ml/min per 1.73 m² undergoing nonemergent computed tomography with intravenous iodinated radiocontrast at an academic VA Medical Center were prospectively identified. Serum creatinine was assessed 48 to 96 h postprocedure to quantify the incidence of CIAKI, and the need for postprocedure dialysis, hospital admission, and 30-d mortality was tracked to examine the associations of CIAKI with these medical outcomes.Results: A total of 421 patients with a median estimated GFR of 53 ml/min per 1.73 m² were enrolled. Overall, 6.5% of patients developed an increase in serum creatinine ≥25%, and 3.5% demonstrated a rise in serum creatinine ≥0.5 mg/dl. Although only 6% of outpatients received preprocedure and postprocedure intravenous fluid, <1% of outpatients with estimated GFRs >45 ml/min per 1.73 m² manifested an increase in serum creatinine ≥0.5 mg/dl. None of the study participants required postprocedure dialysis. Forty-six patients (10.9%) were hospitalized and 10 (2.4%) died by 30-d follow-up; however, CIAKI was not associated with these outcomes.Conclusions: Clinically significant CIAKI following nonemergent computed tomography is uncommon among outpatients with mild baseline kidney disease. These findings have important implications for providers ordering and performing computed tomography and for future clinical trials of CIAKI.The intravascular administration of iodinated contrast media is a well-recognized cause of acute kidney injury, which in turn, is associated with in-hospital morbidity and mortality (1–4). Clinical factors that increase the risk for contrast-induced acute kidney injury (CIAKI) include preexistent kidney disease, diabetes mellitus in the setting of underlying renal impairment, advanced congestive heart failure, intravascular volume depletion, administration of large volumes of contrast, and the use of high-osmolal contrast media (1,5–8). Much of our understanding of the risk factors for, incidence of, and outcomes associated with CIAKI emanate from clinical studies of patients undergoing angiography, particularly coronary angiography. Moreover, most clinical trials of preventive interventions, such as N-acetylcysteine (NAC) and intravenous (IV) fluids, have been conducted in patients undergoing angiographic procedures (9–15). Despite this, expert recommendations for the prevention of CIAKI make little distinction between patients undergoing cardiac catheterization and other contrast-enhanced procedures, or in the status of the patient at the time of the radiographic procedure (outpatient versus hospitalized) in regard to determining patients’ risk level for CIAKI or implementing preventive measures (6,16–18). Additionally, it remains unclear whether the morbidity and mortality that have been associated with CIAKI among hospitalized patients are present among outpatients.A large proportion of patients who receive intravascular iodinated contrast do so when undergoing outpatient computed tomography. The routine assessment of risk status and implementation of preventive interventions, such as IV fluid, are considerably more difficult in patients who undergo elective computed tomography than coronary angiography. The practical and fiscal challenges to systematically administering preprocedure and postprocedure IV fluid to “at risk” patients are substantial, particularly in the outpatient setting. However, to determine the most effective and practical approach to identifying patients at increased risk for CIAKI following computed tomography and implementing preventive care to those most likely to derive benefit, greater clarity is needed on the incidence and clinical sequelae of CIAKI in this patient population. The primary aim of this study was to assess the incidence and outcomes of CIAKI following nonemergent computed tomography in the inpatient and outpatient setting.     

Ring Annuloplasty in Chronic Ischemic Mitral Regurgitation: Encouraging Early and Midterm Results

Ischemic mitral regurgitation, a complication of myocardial infarction, is associated with a poor prognosis and can result in postinfarction congestive heart failure. The preferred treatment of its chronic form is a matter of debate. Herein, we report the early and midterm results in 44 patients with chronic ischemic mitral regurgitation in whom concomitant mitral ring annuloplasty and coronary revascularization were performed at our hospital.We reviewed their medical records. The patients had grades 3/4 and 4/4 chronic ischemic mitral regurgitation, or grade 2/4 regurgitation with left ventricular dilation and low left ventricular ejection fraction. All received circular, flexible annuloplasty rings.Four patients died during the early postoperative period due to low cardiac output (9.1%). At the last follow-up echocardiographic examinations, performed a mean 13.14 ± 4.66 months after the surgical procedures (range, 6–22 mo), the 40 surviving patients were found to have significantly reduced left ventricular end-diastolic (P = 0.029) and end-systolic (P < 0.05) diameters and improved New York Heart Association functional class (P = 0).Despite a risk of residual regurgitation, mitral ring annuloplasty appears to be a good treatment alternative in selected patients who have chronic ischemic mitral regurgitation. We discuss the procedure''s rate of hospital mortality, and its potentially positive impact on survival.Key words: Cardiac surgical procedures, chronic disease, coronary artery bypass/mortality, coronary disease/complications/mortality/surgery, mitral valve/surgery, mitral valve insufficiency/complications/mortality/physiopathology/surgery, myocardial infarction/complications/mortality/physiopathology/surgery, myocardial revascularization, postoperative complications/mortality, prognosisIschemic mitral regurgitation (IMR) is a mechanical complication of myocardial infarction (MI) and a predictor of poor outcome. It is most frequently seen after inferior MI (in 38% of cases) and anteroseptal MI (in 10%).¹ Ischemic mitral regurgitation is clinically divided into 2 forms: acute and chronic. The acute form of IMR develops after an acute post-MI rupture of papillary muscle. Conversely, a widely accepted clinical definition of the chronic form has not yet been agreed upon. Borger and colleagues proposed a definition of the condition in their review.² Several mechanisms are responsible for the development of chronic IMR, including annular dilation; global left ventricular (LV) dilation together with a coaptation defect caused by the traction of the mitral valve leaflets due to the apical, posterior, and lateral displacement of both papillary muscles; and a local malfunction in the LV wall that adjoins a papillary muscle.³ Chronic IMR is found in 10% to 20% of patients with coronary artery disease,⁴ and it is a major cause of congestive heart failure after MI.⁵ Despite such prevalence, surgical intervention to correct IMR remains open to debate, because early hospital mortality rates are high and long-term survival rates are not satisfactory.Substantial improvements have been attained by use of valvular intervention in patients who exhibit heart failure and low LV ejection fraction (LVEF).^6–8 Our current approach is valvular intervention in patients with IMR grades 3/4 and 4/4, and in patients who have grade 2/4 IMR with LV dilation and a low LVEF. Previously, we performed mitral valve replacement (MVR), but we have come to prefer mitral ring annuloplasty (MRA). Here, we present and discuss the early and midterm results in 44 patients who underwent concomitant coronary artery bypass grafting (CABG) and MRA at our institution.     

Revascularization Options in Patients with Chronic Kidney Disease

Cardiovascular disease is the leading cause of death in patients who have chronic kidney disease or end-stage renal disease and are undergoing hemodialysis. Chronic kidney disease is a recognized risk factor for premature atherosclerosis. Unfortunately, most major randomized clinical trials that form the basis for evidence-based use of revascularization procedures exclude patients who have renal insufficiency. Retrospective, observational studies suggest that patients with end-stage renal disease and severe coronary occlusive disease have a lower risk of death if they undergo coronary revascularization rather than medical therapy alone. Due to a lack of prospective studies, however, the relative merits of percutaneous versus surgical revascularization are merely a matter of opinion. Several small, retrospective studies have shown that coronary artery bypass grafting is associated with higher procedural death but better long-term survival than is percutaneous coronary intervention. This difference appears to result from poor long-term results of percutaneous coronary intervention in patients who have chronic kidney disease or end-stage renal disease.Because randomized trials comparing percutaneous coronary intervention and coronary artery bypass grafting have included patients undergoing balloon angioplasty and placement of bare-metal stents, their conclusions are suspect in the era of drug-eluting stents. In this review, we discuss different revascularization options for patients with chronic kidney disease, the outcomes of revascularization procedures, and the risk factors for adverse outcomes.Key words: Angioplasty, transluminal, percutanous coronary; coronary artery bypass; coronary artery bypass, off-pump; creatinine/blood/metabolism; drug-eluting stents; extracorporeal circulation; glomerular filtration rate; kidney failure, chronic; renal dialysis; stents; treatment outcomeThe prevalence of end-stage renal disease (ESRD), defined as renal dysfunction requiring chronic renal replacement therapy, is increasing. In 2007, there were about 341,000 patients with ESRD on hemodialysis and 143,000 patients with transplanted kidneys in the United States.¹ An additional 8% of adults in the U.S. have chronic kidney disease stages 3 and 4 (characterized by a glomerular filtration rate [GFR] between 15 and 60 mL/min/1.73 m²).² The United States Renal Data System (USRDS) projects that, at the current growth rate, the number of patients with ESRD will increase to 534,000 by the year 2020.¹ Within 18 to 24 months of beginning renal replacement therapy, 12% of patients will have an acute myocardial infarction, more than 60% will receive a diagnosis of congestive heart failure, and, by 3 years, 38% will die suddenly, presumably of cardiovascular causes.¹ In chronic kidney disease patients who are not hemodialysis dependent, the risk of dying of cardiovascular disease is greater than the risk of developing ESRD.³ In addition to the traditional risk factors for atherosclerosis,⁴ an abnormal GFR contributes independently to the risk of atherosclerosis-related events in patients with kidney disease.⁵     

PleurX? Catheter for the Management of Refractory Pleural Effusions in Congestive Heart Failure

Pleural effusions that are caused by congestive heart failure and refractory to medical management are rare, and the options for treating them are few and sometimes ineffective. We report here our experience, over a 2-year period, with a novel device, the Denver Biomedical PleurX® pleural catheter, in treating a series of 5 patients who had chronic, refractory, heart-failure–associated pleural effusions. The PleurX catheter is a small-bore chest tube designed to remain in place for prolonged periods, through which drainage of pleural fluid can be performed easily on a daily or less frequent outpatient basis. Placement of the catheter, in our series, was associated with no complications. In all patients, the catheter effectively drained the pleural space initially, thereby controlling the effusions and alleviating New York Heart Association functional class IV symptoms. The catheters remained in place for a period of 1 to 15 months. In 2 of the patients, the catheter was associated with no complications during the time that it remained in place. One of these patients had the catheter removed at heart transplantation, and 1 retained the catheter until death from underlying heart disease. For 1 patient, the catheter resulted in a partially loculated pleural space, and it was removed. In 2 patients, after prolonged use, it was associated with empyema, for which it was removed. We conclude that the PleurX catheter can effectively control refractory congestive-heart-failure–associated pleural effusions temporarily, but that its prolonged use can cause significant complications, most importantly empyema.Key words: Ambulatory care, catheters, indwelling, drainage/methods, heart failure, congestive, pleural effusionPleural effusions are a common complication of congestive heart failure (CHF).^1–4 Standard medical management of CHF, especially with diuretic agents, is generally very effective in treating these effusions.^5,6 For symptomatic effusions that do not respond adequately or rapidly enough to medical management, thoracentesis is typically performed, with excellent results.^5,6 Rarely, however, pleural effusions due to CHF, particularly in the settings of advanced cardiac failure or impaired renal function, prove to be recurrent or refractory to even the most aggressive medical regimens. Efforts to control such effusions have been limited to serial thoracenteses and pleurodesis.^5,6 Serial thoracenteses, depending upon the frequency, are generally unsatisfactory to patients and, of course, the more frequently they are performed, the greater the risk of complication. Although pleurodesis is the preferred alternative to serial thoracenteses, it also has serious potential limitations and complications,^7–11 whether performed by the traditional “closed” chest tube technique or by state-of-the-art video-assisted thoracoscopic surgery (VATS). Therefore, alternative solutions to this very difficult clinical problem are needed.¹²The PleurX® Pleural Catheter (Denver Biomedical, Inc., part of Cardinal Health, Inc.; Golden, CO) was recently developed for use in patients who cannot tolerate VATS pleurodesis or who have malignant pleural effusions that traditional, closed pleurodesis often cannot control adequately.¹³ The PleurX catheter is essentially a small-bore chest tube that is designed to remain in place for prolonged, intermittent drainage of the pleural space through a one-way valve. The PleurX has proved to be very effective for such drainage, and complication rates have been relatively low.^13–16We hypothesized that the PleurX might be an effective tool for the medical management of refractory pleural effusions caused by CHF. We therefore placed the catheter in 5 of our CHF patients who were poor candidates for traditional pleurodesis. Herein we report our experience with the PleurX catheter, which we believe to be the 1st use of a chronically indwelling catheter system for the management of recurrent pleural effusions in CHF.     

Low Pulse Pressure as a Predictor of Death in Patients with Mild to Advanced Heart Failure

The prognostic value of pulse pressure has been investigated in heart-failure patients. Low pulse pressure in advanced heart failure and high pulse pressure in mild heart failure have been separately linked to increased mortality rates. We prospectively investigated an association between pulse pressure and 2-year cardiovascular death in an entire heart-failure population.We prospectively enrolled 225 heart-failure patients (New York Heart Association [NYHA] functional class, I–IV; mean age, 56.5 ± 12.3 yr; 188 men). The patients'' blood pressures were measured in accordance with recommended guidelines. Pulse pressures were calculated as the difference between systolic and diastolic blood pressure values. The patients were monitored for a mean period of 670 ± 42 days for the occurrence of cardiovascular death.All patients were divided into quartiles according to their pulse pressures (<35, 35–45, 46–55, and >55 mmHg). Pulse pressure decreased as NYHA class worsened (P <0.001). Patients in the <35-mmHg quartile had the lowest plasma sodium concentrations, left ventricular ejection fractions, and systolic myocardial velocities upon echocardiography; and the highest left ventricular dimensions, early diastolic/late diastolic filling velocity ratios, and peak early/peak late diastolic myocardial velocity ratios. Pulse pressure independently predicted death in the patients with advanced heart failure and in the entire population. Upon receiver operating characteristic analysis, a 30-mmHg cutoff value for pulse pressure predicted death with 83.7% sensitivity and 79.7% specificity.Pulse pressure is easily calculated and enables the prediction of cardiovascular death in patients with mild to advanced heart failure. Pulse pressure can be used reliably as a prognostic marker in clinical practice.Key words: Blood pressure/physiology, cardiovascular diseases/mortality/physiopathology, epidemiologic methods, heart failure/epidemiology/etiology/physiopathology, multivariate analysis, predictive value of tests, prospective studies, pulse/physiology, reference values, risk factorsPulse pressure (PP) is the difference between systolic and diastolic blood pressure (BP) values. Pulse pressure markedly rises after the 5th decade of life, due to arterial stiffening with increasing age.^1,2 Several studies have shown a close relationship between high PP and the occurrence of cardiovascular (CV) death.^3-5 Furthermore, high PP is a risk factor for the development of coronary heart disease, myocardial infarction, and heart failure in normotensive and hypertensive persons.^6-10Data regarding the prognostic value of PP in patients with heart failure are limited and controversial. The importance of PP was investigated in 2 large studies. The SAVE¹¹ (Survival and Ventricular Enlargement) trial revealed a worse prognosis in patients with high PP and symptomatic or asymptomatic left ventricular (LV) systolic dysfunction. The SOLVD¹² (Studies of Left Ventricular Dysfunction) trial found that high PP independently predicted total and CV death in mild heart failure. However, in both studies, patients in New York Heart Association (NYHA) functional classes I and II constituted most of the population, and few patients had advanced heart failure (NYHA classes III and IV). In other studies involving patients with advanced heart failure, low PP was associated with high CV mortality rates.^13-16 We believed that further study was warranted in order to elucidate the prognostic value of PP in an entire heart-failure population. Accordingly, we investigated the association between PP and 2-year CV death in patients in whom the severity of heart failure ranged from mild to advanced.     

Pericardial Fat Necrosis: A Review and Update

A previously healthy middle-aged person presents with excruciating left-sided chest pain of 6 hours'' duration. The pain has come on abruptly, without warning, and is located in the lower part of the chest anteriorly. It radiates to the neck and left shoulder and worsens on deep inspiration. The patient appears seriously ill, with tachypnea, tachycardia, and diaphoresis. Otherwise, the physical examination is unremarkable. The electrocardiogram shows sinus tachycardia. Results of conventional blood studies and the chest radiograph are within normal limits. Three days later, a follow-up chest radiograph shows a 3.5 × 4-cm mass adjacent to the left side of the heart near the diaphragm.This hypothetical case illustrates the typical presentation of a rare but important benign disease—pericardial fat necrosis (PFN). At least 23 cases of PFN have been documented in the English-language medical literature since Jackson, Clagett, and McDonald described the condition in 1957.^1–17 Textbooks of internal medicine^18–22 and cardiology^23–25 offer nothing on this ailment, and only 1²⁶ of 3^26–28 books devoted solely to the pericardium mentions it. As a result, PFN remains little known and poorly appreciated. Yet, early in its course, PFN characteristically is mistaken for a serious disease, particularly myocardial infarction^1–3,10 or pulmonary embolism.^1,8,10,13 Later, it uniformly mimics a pericardial cyst or a pericardial or pulmonary neoplasm. Misdiagnosis and mismanagement are inevitable, therefore, if one is not familiar with this unique clinicoradiologic entity. Hence, this review.

Clinical Features

Pericardial fat necrosis classically strikes suddenly, without warning. All of the victims reported to date—15 men and 8 women—were in good health at the time PFN began. They ranged in age from 23 to 67 years (mean age, 49.2 yr). Five of the men^1–3,6 and 2 of the women^11,12 were white and 1 of the women was black.¹³ Race was not recorded for the remaining 15 patients.Severe chest pain, typically pleuritic, is the initial manifestation. It was left-sided in 15 patients,^{1–3,5–7,9–11,13,14,16} right-sided in 5,^1,4,8,10,12 present but not further described in 1,¹⁶ absent in 1,¹⁷ and not mentioned in 1.¹⁵ The pain is located anteriorly near the diaphragm and radiates at times to the neck, shoulder, upper arm, axilla, or back. It lasts several days to a week or so, but can recur with less intensity for up to a year.^1,10 Fever and cough are not features of PFN.If examined soon after onset of the chest pain, the patient is dyspneic, with tachypnea, tachycardia, and diaphoresis. One patient was hypotensive at admission,³ 2 had a pericardial friction rub,^3,7 and 3 others had marked tenderness to palpation over or near the precordium.^5,6,10 By contrast, if several days or more elapse before the patient comes under observation, the physical examination usually gives normal findings.Electrocardiographic Observations. The electrocardiogram characteristically is normal. Occasionally, it shows tachycardia, nonspecific ST- or T-wave changes suggesting ischemia, or findings consistent with resolving pericarditis.^8,13,14 In 1 case, it showed right bundle branch block.¹¹

Imaging Results

Chest radiographs obtained during the first few days of the illness may show no abnormality. Thereafter, a mass invariably appears in or near the cardiophrenic angle on the side of the chest pain. The mass is always located anteriorly and is almost always contiguous with the cardiac silhouette. In 1 case, however, it extended between the lingula and left lower lobe¹⁰; in another, it overlay the left hemidiaphragm in the area of the interlobar fissure¹; and in another, it was distinctly separate from the heart.⁷ Finding such a mass on the chest radiograph always raised concern for a pericardial cyst or a pericardial or pulmonary neoplasm.Computed tomography (CT) helps determine the nature and exact location of the chest mass.^12–16,17 From density measurements, one can infer that the mass consists of fat; but CT cannot always distinguish between a benign and malignant fatty tumor, especially when stranding is present within the fat.^13,16 In such cases, operative intervention might still be indicated to establish the precise diagnosis.Magnetic resonance imaging performed in 2 patients confirmed the CT findings of fat with dense stranding.^14,16Gallium-67 scintigraphy in a patient with unexplained hemoptysis incidentally showed increased gallium uptake in the pericardial fat.¹⁵ Subsequent biopsy of the pericardial fat showed necrosis but no evidence of malignancy.

Miscellaneous Studies

Pleural effusion occurred in 4 patients. Thoracentesis yielded only a small amount of bloody fluid in 1 case,¹ “did not demonstrate any evidence of malignancy and the bacterial culture was negative” in another case,¹⁴ and was not mentioned in the third case.¹⁵ In the fourth case, thoracentesis disclosed a pH of 7.58; erythrocytes, 13,600/mm³; leukocytes, 5,000/mm³ (64% segmented neutrophils, 13% lymphocytes, and 24% monocytes); glucose, 139 mg/dL; protein, 4.6 g/dL; and lactate dehydrogenase, 167 U/mL.¹³Transthoracic and transesophageal echocardiography performed in 1 patient¹⁷ demonstrated a 5-cm, ovoid, solid pericardial mass compressing the right side of the heart.Other investigations that were noncontributory included the total and differential leukocyte counts, erythrocyte sedimentation rate, serum amylase and electrolytes, cardiac enzymes, barium swallow and barium enema, complete metastatic workup, arterial blood gas determination, ventilation/perfusion lung scan, bronchography, bronchoscopy with cytologic washings, pulmonary function tests, and pulmonary angiography.^{4,7,8,12,13,17}

Diagnosis

In 22 of the 23 cases, histologic examination of biopsied or (most often) resected tissue proved PFN. The sole exception was a case reported 5 years ago, in which the clinical, radiographic, and CT findings prompted a tentative diagnosis of PFN.¹⁶ With symptomatic treatment, the chest pain resolved at 1 week, and the chest radiograph 2 months later showed that the paracardiac density had disappeared. A follow-up chest CT at 2 months also showed a marked decrease in size and thickness of the pericardial lesion.

Surgical and Histologic Findings

After nondiagnostic workups, sometimes extensive, 21 of the 23 patients underwent exploratory thoracotomy. At operation, the typical finding was an inflammatory mass involving the parietal pericardial fat pad; masses varied from 1.5 cm in size⁹ to 10 × 7.5 × 3 cm in size.³ The pathologic features bore close resemblance to those of infarcted epiploic appendices and to fat necrosis in the breast.⁸ Lesions removed early in the clinical course showed a central focus of necrotic fat cells encompassed by macrophages with intense neutrophilic infiltration.¹² Specimens removed later in the clinical course showed considerable fibrosis as well. In 1 case, calcifications were also present.¹⁷ Resection of the diseased tissue effected a cure in every case, with follow-ups for as long as 19 years.¹⁰

Pathogenesis

The cause of PFN remains speculative. In 2 patients, the mass was attached to the heart by a pedicle, acute torsion of which might have triggered the necrosis.^1,5 A pre-existing structural abnormality of the adipose tissue, such as lipoma or hamartoma, might make the tissue vulnerable to the trauma of a beating heart and moving diaphragm.^4,6,17 Two cases lend credence to this possibility: in 1, lipomatosis abutted the right atrium¹⁷; in the other, the resected specimen was histologically consistent with a lipoma showing fat necrosis.⁴ In the circumstance of extreme lifting efforts before⁶ or during³ onset of the chest pain, rapid changes in intravascular pressure associated with the Valsalva maneuver might cause hemorrhage into the loosely supported adipose tissue of the pericardium. The hemorrhage might, in turn, initiate the necrosis.⁶ Although the original report on PFN listed obesity as a probable prerequisite for the disease,¹ only 8 of the 20 patients in subsequent reports were said to be obese.^8–11,14 Evidence of recent or concomitant infection, acute pancreatitis, or any other disease has been absent in every case.