Exercise-induced torsional dyssynchrony relates to impaired functional capacity in patients with heart failure and normal ejection fraction.

BACKGROUND: Left ventricular (LV) systole and diastole are intimately dependent on myocardial torsion, which involves coupling between myocardial rotation (twisting in systole and untwisting in diastole) and longitudinal motion. Heart failure with normal ejection fraction (HFNEF) is known to involve exercise-induced wall motion abnormalities, but torsion on exercise has not been explored. We hypothesised that torsional dyssynchrony may also be involved and be exaggerated by exercise. METHODS AND RESULTS: 67 patients (age 73±7 years, 45 female) with HFNEF and 38 controls underwent cardiopulmonary exercise testing and echocardiography at rest and on supine exercise. Analysis of three plane motions was performed using speckle tracking and tissue Doppler imaging. Torsional dyssynchrony was quantified as the SD of the time to peak systolic motion (SDSM) (basal and apical rotation, longitudinal and radial displacement); the time difference between peak twist and peak longitudinal displacement (twist-longitudinal motion delay, TLMD) and the ratio of untwist to longitudinal extension (UT:LE). At rest, HFNEF patients had similar SDSM, TLMD and UT:LE compared with controls. Exercise was associated with significantly more dyssynchrony in the HFNEF patients (SDSM 38.8±27.6 ms vs 25.9±15.5 ms, p=0.02; TLMD 28.4±46.2 ms vs 2.9±31.2 ms, p=0.005 and UT:LE 10.4±15.3 vs 3.3±3.8, p=0.022). The SDSM correlated positively with LV wall thickness (r=0.31, p=0.015) and negatively with peak oxygen consumption (r=-0.299, p=0.01) and changes in stroke volume on exercise (r=-0.371, p=0.001). CONCLUSIONS: HFNEF involves exercise-induced torsional dyssynchrony in systole and diastole, which relates to LV hypertrophy as well as exercise capacity.

Mitral annular plane systolic excursion on exercise: a simple diagnostic tool for heart failure with preserved ejection fraction.

AIMS: Current guidelines for the diagnosis of heart failure with normal or preserved ejection fraction (HFpEF) are based on measurements at rest. However, in HFpEF ventricular dysfunction is more apparent on exercise. We hypothesized that Mitral annular plane systolic excursion (MAPSE) which is easy to acquire on exercise could be used to detect occult left ventricular (LV) impairment. METHODS AND RESULTS: Cardiopulmonary exercise testing and 2D-Doppler echocardiography were performed at rest and on exercise. MAPSE was assessed by using M-mode (apical four-chamber view). Sixty-two patients with HFpEF [LV ejection fraction (LVEF)=60 ± 7%] with reduced VO(2) max (18.6 ± 5.2 mL/min/kg) and 36 control subjects (LVEF=62 ± 7%, VO(2) max 29.4 ± 4.8 mL/min/kg) were studied. MAPSE at rest was significantly lower in patients (10.9 ± 2.1 vs. 12.1 ± 2.2 mm in controls, P= 0.008) which was even more pronounced on exercise (12.0 ± 2.2 mm and 16.2 ± 2.7 mm, respectively, P< 0.001). At rest MAPSE correlated with longitudinal strain (r = 0.432, P= 0.001), peak systolic myocardial velocity (r = 0.545, P< 0.001), and early diastolic myocardial velocity (r = 0.322, P= 0.02) and on exercise with LV apical rotation (r = 0.582, P< 0.001), longitudinal strain (r = 0.589, P< 0.001), and myocardial tissue velocities (P< 0.001). The area under the receiver operating characteristic curve for MAPSE was 0.655 (confidence interval 0.540-0.770) at rest and 0.901 (confidence interval 0.835-0.967) on exercise, to differentiate between patients and controls. CONCLUSION: Mitral annular plane systolic excursion at rest and on exercise correlates well with more sophisticated measurements of ventricular function in HFpEF patients. It is potentially a useful and easily acquired measurement, especially on exercise, for the diagnosis of HFpEF.

Abnormal left ventricular function occurs on exercise in well-treated hypertensive subjects with normal resting echocardiography.

OBJECTIVES: This study tests the hypothesis that patients with treated hypertension with well-controlled blood pressure, without ventricular hypertrophy and normal resting echocardiography, may have abnormalities of ventricular function that are apparent only on exercise and contribute to symptoms of exertional dyspnoea. METHODS: Patients with hypertension with well-controlled blood pressure on medication and normal baseline echocardiography underwent cardiopulmonary exercise testing to determine their peak oxygen consumption (Vo(2)(max)), followed by rest and submaxinal supine exercise echocardiography (standard, tissue Doppler and speckle tracking). RESULTS: 30 patients with treated hypertension with a history of exertional dyspnoea (mean age 71+/-8 years; 18 women) and 22 age-matched healthy controls (70+/-6 years; 16 women) had rest and exercise images of sufficient quality for analysis. Both groups had comparable standard echocardiographic findings at rest. On exercise, the patients had reduced systolic longitudinal function (reserve index 0.97+/-1.34 vs 2.32+/-1.24, p=0.001), delayed early untwisting (20.4+/-7.6 vs 30.6+/-7.8%, p=0.001) and reduced ventricular suction (velocity propagation 10.6+/-10.9 vs 24.5+/-12.2 m/s, p<0.001) compared with healthy controls, which correlated with significantly reduced Vo(2)(max). CONCLUSION: Patients with treated hypertension with normal resting echocardiography can have exercise limitation associated with widespread systolic and diastolic left ventricular dysfunction on exercise. Normal resting echocardiography does not preclude the presence of significant functional abnormalities on exercise that can contribute to symptoms.

The pathophysiology of heart failure with normal ejection fraction: exercise echocardiography reveals complex abnormalities of both systolic and diastolic ventricular function involving torsion, untwist, and longitudinal motion.

OBJECTIVES: The purpose of this study was to test the hypothesis that in heart failure with normal ejection fraction (HFNEF) exercise limitation is due to combined systolic and diastolic abnormalities, particularly involving ventricular twist and deformation (strain) leading to reduced ventricular suction, delayed untwisting, and impaired early diastolic filling. BACKGROUND: A substantial proportion of patients with heart failure have a normal left ventricular ejection fraction. Currently the pathophysiology is considered to be due to abnormal myocardial stiffness and relaxation. METHODS: Patients with a diagnosis of HFNEF and proven cardiac limitation by cardiopulmonary exercise testing were studied by standard, tissue Doppler, and speckle tracking echocardiography at rest and on submaximal exercise. RESULTS: Fifty-six patients (39 women; mean age 72 +/- 7 years) with a clinical diagnosis of HFNEF and 27 age-matched healthy control subjects (19 women; mean age 70 +/- 7 years) had rest and exercise images of sufficient quality for analysis. At rest, systolic longitudinal and radial strain, systolic mitral annular velocities, and apical rotation were lower in patients, and all failed to rise normally on exercise. Systolic longitudinal functional reserve was also significantly lower in patients (p < 0.001). In diastole, patients had reduced and delayed untwisting, reduced left ventricular suction at rest and on exercise, and higher end-diastolic pressures. Mitral annular systolic and diastolic velocities, systolic left ventricular rotation, and early diastolic untwist on exercise correlated with peak VO(2)max. CONCLUSIONS: In HFNEF there are widespread abnormalities of both systolic and diastolic function that become more apparent on exercise. HFNEF is not an isolated disorder of diastole.

Reversible pulmonary hypertension in heart transplant candidates: to transplant or not to transplant.

BACKGROUND: Pulmonary hypertension (PHT), defined as a pulmonary vascular resistance (PVR) greater than 2.5 Wood units [WU] and(or) transpulmonary gradient (TPG) greater than 12 mm Hg, is a risk factor for mortality in cardiac transplantation due to elevated postoperative right heart failure. Orthotopic heart transplantation is possible if PVR could be reversed below 2.5 WU and TPG below 12 mm Hg. We show the Muenster experience from the last 10 years. METHODS: From April 1996 to December 2005 all cardiac transplant recipients separated into patients with and without PHT were included. All patients with PHT had successful reduction (PVR < or = 2.5 WU and TPG < or = 12 mm Hg) using prostaglandin I2 or E1. Posttransplant early and late mortality and incidence of right heart failure were studied. RESULTS: Two hundred seventeen patients were included in this study. Of these, 168 had normal pulmonary pressures (non-PHT group), 49 (22.6%) had reversible PHT (rev-PHT group). Mean PVR was 1.6 +/- 1.1 WU vs 2.1 +/- 1.1 WU (p < 0.01; non-PHT vs rev-PHT) and mean TPG 8.0 +/- 1.9 mm Hg vs 10.6 +/- 4.1 mm Hg (p = not significant [NS]). Thirty-day survival after orthotopic cardiac transplantation was 85% vs 78% (p = 0.150) and 10 year survival 63% vs 61% (p = NS). Right heart failure during the first 30 days after transplantation occurred in 27% in the non-PHT group and in 64% in the rev-PHT group (p = 0.035). However, in patients transplanted after 2001 it did not appear. CONCLUSIONS: Cardiac transplant candidates with reversible PHT have still significantly elevated pulmonary pressures compared with patients without PHT. Despite a significantly higher risk of right heart failure, long-term survival after orthotopic cardiac transplantation was not affected.

Does nasal cocolonization by methicillin-resistant coagulase-negative staphylococci and methicillin-susceptible Staphylococcus aureus strains occur frequently enough to represent a risk of false-positive methicillin-resistant S. aureus determinations by molecular methods?

By analyzing the colonization of the anterior nares in cardiothoracic surgery patients on admission, nasal cocolonization by methicillin-susceptible Staphylococcus aureus and methicillin-resistant coagulase-negative staphylococci was detected in 8/235 (3.4%) specimens. Consequently, in a low-methicillin-resistant S. aureus (MRSA) setting, a molecular MRSA screening test targeting the mecA gene and an S. aureus-specific gene in parallel and applied directly to clinical specimens would be associated with an unacceptable positive predictive value of about 40%.

Partial left ventriculectomy and mitral valve repair: favorable short-term results in carefully selected patients with advanced heart failure due to dilated cardiomyopathy.

BACKGROUND: Because of the scarcity of donor hearts, surgical alternatives to heart transplantation, such as partial left ventriculectomy (PLV), were introduced for treatment of advanced heart failure. Here, we report our experience with this procedure performed in combination with mitral valve repair. METHODS: Twelve patients with dilated cardiomyopathy (DCM), New York Heart Association (NYHA) class exceeding III on maximal medical therapy, cardiac index of 2.5 liter/min/m2 or less, VO2max of 14 ml/kg/min or less, left ventricular end-diastolic diameter (LVEDD) of 7.0 cm or more, and grade II or greater mitral incompetence, were selected for PLV and mitral valve reconstruction (MVR). Echocardiography, hemodynamics, spiroergometry, and clinical assessment were performed before and 1 year after the operation. RESULTS: One-year survival was 83.3%. All 10 surviving patients were free from failure of the procedure 1 year post-operatively. From pre-operatively to 1 year post-operatively, NYHA functional class improved from 3.3 +/- 0.3 to 1.9 +/- 0.2 (p < 0.001), cardiac index increased from 2.0 +/- 0.2 liter/min/m2 to 2.9 +/- 0.2 liter/min/m2 (p < 0.001), stroke volume index from 25.9 +/- 4.8 ml/m2 to 40.3 +/- 7.3 ml/m2 (p = 0.008), and VO2max from 10.9 +/- 2.4 ml/kg/min to 16.0 +/- 3.6 ml/kg/min (p = 0.016), whereas LVEDD decreased from 8.4 +/- 0.6 cm to 6.6 +/- 0.3 cm (p < 0.001), left ventricular end-systolic diameter from 6.8 +/- 0.8 cm to 5.3 +/- 0.5 cm (p < 0.001), and mitral incompetence from 2.4 +/- 0.6 to 0.9 +/- 0.6 (p < 0.001). Pulmonary pressures and fractional shortening did not change significantly (p > 0.05). Four patients received an implantable cardioverter/defibrillator as a result of their pathologic electrophysiologic examination. CONCLUSIONS: In carefully selected patients, PLV combined with MVR achieves short-term results comparable to that after heart transplantation. However, long-term results and multicenter evaluation will be needed to define its place in the treatment of advanced heart failure.

First clinical experience with the Incor left ventricular assist device.

BACKGROUND: The Incor (Berlin Heart AG, Germany) is a small (200 g), implantable, magnetically accentuated axial flow pump (non-pulsatile flow) designed to support the left ventricle for extended periods of time. We report on the first single-center clinical experience with this device. METHODS: The Incor was studied in 15 consecutive patients (10 men, 5 women), 24 to 59 years of age. Underlying heart disease was end-stage ischemic heart disease (n = 5), acute myocardial infarction (n = 4), dilated cardiomyopathy (n = 3), acute myocarditis (n = 2) and Chagas disease (n = 1). All patients were in New York Heart Association (NYHA) Class IV heart failure. Four patients had prior open heart surgery. Implantation via cannulation of the left ventricular apex and the ascending aorta was elective in 6 patients and on an emergency basis in 9. RESULTS: No early bleeding complications were seen, but late bleeding occurred in 4 patients. Minor cerebral thromboembolic events with transient neurologic symptoms occurred in 3 patients; severe stroke had to be treated in 1 patient. Systemic emboli were seen in 2 patients. Thrombus-related pump dysfunction was suspected in 3 patients, and managed by intensifying anti-coagulation. Five patients were successfully transplanted after a support interval of 90 to 156 days; 1 patient could be weaned from the system after 171 days. Six patients died during support, 9 to 63 days after device implantation. The remaining 3 patients are still under support, with excellent quality of life. CONCLUSIONS: The Incor is a left ventricular assist device (LVAD) with transplant and adverse event rates comparable to those of other modern ventricular support devices. Its advantages include the small pump chamber, the virtual absence of device-related infections, and the extraordinary convenience during implantation and explantation.

Ischemic preconditioning by unstable angina reduces the release of CK-MB following CABG and stimulates left ventricular HSP-72 protein expression.

BACKGROUND AND AIM: Whether the CK-MB reducing effect of ischemic preconditioning (IP) by unstable angina within 24 to 48 hours before CABG is achieved by early or by delayed preconditioning of left ventricular myocardium in humans is unknown. We investigated whether IP is associated with phosphorylation of p38 MAPK (characteristic for early preconditioning) or with increased protein expression of HSP-72 (characteristic for delayed preconditioning) at the time of CABG in patients. METHODS: Nineteen patients were grouped according to the occurrence of ischemic episodes within 48 hours before CABG. The patients without angina were assigned to the control group (CON, n = 10) whereas patients who had experienced angina within 48 hours before CABG were assigned to the preconditioned group (IP, n = 9). The effect of IP on the CABG induced maximal release of creatine kinase (CK) and CK-MB was examined. Left ventricular biopsy specimens taken immediately before cross clamping from ischemic (ISCH) and from reference (REF) areas were processed to analyze p38 MAPK phosphorylation and HSP-72-protein expression. RESULTS: While IP significantly reduced CK-MB (18.7 +/- 1.3 vs. 13.8 +/- 1.5 U/L, mean +/- SEM, p < 0.05), it only tended to reduce CK (292.7 +/- 32.8 vs. 274.1+/-31.1 U/L, p = NS, mean +/- SEM). CK-MB release for any given cross-clamp time was significantly reduced by IP (regression lines: CON, y= 0.4x+ 2, r= 0.8; IP, y= 0.1x+ 10, r= 0.2; p < 0.01, ANCOVA). There was no effect of IP on left ventricular p38 MAPK phosphorylation. IP increased left ventricular HSP-72-protein expression in ischemic areas when compared to reference areas (1.78 +/- 0.35 vs. 2.58 +/- 0.65, REF vs. ISCH, PhosphorImager units x10(6), mean +/- SEM, p < 0.05, ANCOVA). CONCLUSIONS: Thus, in the human left ventricular myocardium there is a second window of protection lasting for at least 48 hours, while at that time the early phase of preconditioning has already gone.

Electrocardiography and Doppler echocardiography for risk stratification in patients with chronic heart failure: incremental prognostic value of QRS duration and a restrictive mitral filling pattern.

OBJECTIVES: This prospective study tested whether Doppler echocardiographic variables add incremental value to QRS duration in determining the prognosis of patients with chronic heart failure (CHF) and systolic dysfunction. BACKGROUND: Diastolic dysfunction frequently is observed in patients with CHF, but its prognostic impact relative to that of QRS duration is unknown. METHODS: A total of 193 patients with CHF and an ejection fraction <45% were enrolled prospectively. Echo measurements included left ventricular dimensions/volumes, ejection fraction, mitral early/late diastolic velocity ratio, deceleration time, and tissue Doppler mitral annular velocities. The mitral filling pattern was classified as either restrictive (RFP) or nonrestrictive. A cardiac event (cardiac death or urgent cardiac transplantation) was defined as combined study end point. RESULTS: During a follow-up of 385 +/- 270 days, 24 patients suffered an event (cardiac death, n = 21; urgent transplantation, n = 3). The RFP, QRS duration, left ventricular systolic diameter, and mitral annular early diastolic velocity were independent predictors of an event. In patients with QRS duration >144 ms, the outcome was markedly poorer in the presence of RFPs as compared with their absence. Similarly, despite a QRS duration

Aminoterminal pro type B natriuretic peptide as a predictive and prognostic marker in patients with chronic heart failure.

BACKGROUND: B-type natriuretic peptide (BNP) is released from the cardiac ventricles in response to increased wall tension. We studied the relation of NT-proBNP to Heart Failure Survival Score (HFSS) and New York Heart Association (NYHA) class in patients with chronic heart failure (CHF). We also studied the impact for recipient selection for cardiac transplant and assessed it as a predictive and prognostic marker of CHF. METHODS: A total of 550 patients with dilative cardiomyopathy (n = 323), and coronary artery disease (n = 227) were prospectively examined. All patients underwent spiroergometry, echocardiography, right heart catheterization, and electrocardiogram. Routine blood levels and NT-proBNP were measured. The clinical selection for cardiac transplant candidates was adjudicated by 2 independent cardiologists who were blinded to the results of NT-proBNP assays. Clinical outcome and predictive power of NT-proBNP were analyzed. RESULTS: NT-proBNP levels in patients clinically considered for cardiac transplantation were significantly higher (2293 ng/ml vs 493 ng/ml; p < 0.001). The receiver operating characteristic (ROC) analysis regarding transplant candidacy showed an area under the ROC curve (AUC) of 0.84 +/- 0.01 for HFSS, 0.86 +/- 0.001 for NYHA, and 0.96 +/- 0.01 for NT-proBNP. Patients with increasing NT-proBNP levels or remaining elevated levels despite adequate heart insufficiency treatment were maintained with left ventricular assist device implantation (n = 10) or urgent heart transplantation (n = 2). Patients with NT-proBNP levels above 5000 pg/ml had a mortality rate of 28.4% per year. Twenty-eight patients died during the observation period; all these patients were within NYHA Classes 3 and 4 (NT-proBNP 5423 +/- 423 ng/ml). CONCLUSIONS: NT-proBNP discriminates patients at high likelihood of being a candidate for transplantation and provides prognostic informations in patients with CHF. NT-proBNP levels above 5000 pg/ml at admission were associated with death, and these levels markedly discriminated candidates for left ventricular assist devices or urgent transplantation.

Analysis of platelet function during left ventricular support with the Incor and Excor system.

Improvements in pump technology and the scarcity of donor organs have led to an increased use of mechanical assist devices, but the problem of thromboembolism has still not been solved. We report on our initial experience with sequentially analyzing platelet function in patients provided with the Incor left ventricular assist device (LVAD) and the Excor LVAD system. Thirteen patients 5 to 61 years old with acute or end-stage heart failure were included in a pilot study. Five of the 10 Incor patients underwent LVAD placement under emergency conditions, and 5 were electively scheduled for surgery. All 3 patients with an Excor device had been connected to an extracorporeal membrane oxygenation system prior to insertion of the device. An anticoagulation protocol including heparin, aspirin, and clopidogrel was employed, and the patients were closely monitored with a special platelet analyzing system that allows dose optimization for antiplatelet drugs. Initial platelet function was normal in only 2 patients (15%). During a follow-up period of 1770 days (cumulative >4.8 years), no early (<30 days) bleeding complications related to device implantation occurred. Late cerebral thromboembolic events were noted in 3 patients. One patient experienced severe stroke mandating neurosurgery during mechanical assist, and 1 patient experienced systemic embolism. The PAP platelet analyzer offers a cheap and reliable alternative to the more expensive thromboelastography method for adequately surveying the efficacy of aspirin and clopidogrel treatment, even if late thromboembolic events cannot be prevented.