Association between long-term prescription of febuxostat and the progression of heart failure with preserved ejection fraction in patients with hypertension and asymptomatic hyperuricemia.

Both hypertension and hyperuricemia are closely associated with the morbidity and mortality of heart failure. This study was designed to evaluate the influences of long-term xanthine oxidase inhibitor (febuxostat) prescription on left ventricular hypertrophy (LVH), left ventricular (LV) diastolic function, and new-onset heart failure with preserved ejection fraction (HFpEF) in these patients. Using a propensity score matching of 1:2 ratio, this retrospective claims database study compared febuxosatat prescription (n = 96) and non-urate-lowering therapy (n = 192) in patients with hypertensive left ventricular hypertrophy (LVH) and asymptomatic hyperuricemia. With a follow-up of 36 months, febuxostat significantly decreased the level of serum uric acid as well as generated more prominent improvement in LVH and LV diastolic function. Besides, the new-onset symptomatic HFpEF occurred in 2 of 96 patients in febuxostat group and 13 of 192 patients in non-urate-lowering group (P = 0.091). No increased risk for major adverse cardiovascular events in patients prescribed with febuxostat was noted. In conclusion, long-term febuxostat exposure was associated with protective effects in terms of LVH or LV diastolic dysfunction in patients with hypertensive LVH and asymptomatic hyperuricemia. Febuxostat also displayed a trend for reduced risk of new-onset HFpEF in this population.

Results of performing or not cardiac resynchronization therapy for live assessment of LV function and mechanical systole synchrony using gated myocardial perfusion imaging and real-time three-dimensional echocardiography. Seven months follow-up.

We studied a 50 years old male patient who underwent cardiac resynchronization therapy on and off (CRT-on and CRT-off) for assessment of left ventricular (LV) function and mechanical systole synchrony using gated myocardial perfusion imaging (gMPI) and real-time three-dimensional echocardiography (RT3DE). The patient was reexamined after seven months. The comparison of these two modalities showed consistent results on assessing both the CRT-on and CRT-off conditions. This result may indicate that an immediate synchronization parameter change during CRT-on may be valuable for predicting response to CRT surgery.

Assessment of Diastolic Function in Single-Ventricle Patients After the Fontan Procedure.

BACKGROUND: Patients with functional single ventricles after the Fontan procedure have abnormal cardiac mechanics. The aims of this study were to determine factors that influence diastolic function and to describe associations of diastolic function with current clinical status. METHODS: Echocardiograms were obtained as part of the Pediatric Heart Network Fontan Cross-Sectional Study. Diastolic function grade (DFG) was assessed as normal (grade 0), impaired relaxation (grade 1), pseudonymization (grade 2), or restrictive (grade 3). Studies were also classified dichotomously (restrictive pattern present or absent). Relationships between DFG and pre-Fontan variables (e.g., ventricular morphology, age at Fontan, history of volume-unloading surgery) and current status (e.g., systolic function, valvar regurgitation, exercise performance) were explored. RESULTS: DFG was calculable in 326 of 546 subjects (60%) (mean age, 11.7 ± 3.3 years). Overall, 32% of patients had grade 0, 9% grade 1, 37% grade 2, and 22% grade 3 diastolic function. Although there was no association between ventricular morphology and DFG, there was an association between ventricular morphology and E', which was lowest in those with right ventricular morphology (P < .001); this association remained significant when using Z scores adjusted for age (P < .001). DFG was associated with achieving maximal effort on exercise testing (P = .004); the majority (64%) of those not achieving maximal effort had DFG 2 or 3. No additional significant associations of DFG with laboratory or clinical measures were identified. CONCLUSIONS: Assessment of diastolic function by current algorithms results in a high percentage of patients with abnormal DFG, but few clinically or statistically significant associations were found. This may imply a lack of impact of abnormal diastolic function on clinical outcomes in this cohort, or it may indicate that the methodology may not be applicable to pediatric patients with functional single ventricles.

Cardiovascular Health Status and Incidence of Heart Failure in the Framingham Offspring Study.

BACKGROUND: The American Heart Association Cardiovascular Health (CVH) score is inversely associated with cardiovascular disease, but its relations to cardiac remodeling traits and heart failure (HF) incidence have not been examined. METHODS AND RESULTS: A 14-point score was constructed for each participant based on the presence of poor, intermediate, or ideal status on each of the 7 CVH metrics (ideal score=14). We related the CVH score to echocardiographic traits cross-sectionally and to HF incidence prospectively in the Framingham Offspring Study. In age- and sex-adjusted models, a higher CVH score was associated with lower left ventricular (LV) mass, LV wall thickness, LV diastolic dimension, and left atrial dimension (P<0.01 for all; n=2392; mean age, 58 years; 56% women), and with a 12% to 15% lower odds of prevalent LV concentric remodeling and concentric hypertrophy, respectively (P<0.0001 for both). On follow-up (mean, 12.3 years), 188 incident HF events were observed in 3201 participants (mean age, 59 years; 53% women). In age- and sex-adjusted Cox proportional hazard models, the CVH score was inversely associated with HF incidence (hazard ratio per 1-point higher CVH score, 0.77; 95% confidence interval, 0.72-0.83). This association was partially attenuated upon adjustment for LV mass and interim myocardial infarction (hazard ratio, 0.84; 95% confidence interval, 0.76-0.93), and it was consistent for HF with preserved and reduced ejection fractions. CONCLUSIONS: In our community-based sample, comprised predominantly of middle-aged white individuals of European descent, better CVH was associated with lower HF incidence, in part due to a lower prevalence of adverse cardiac remodeling.

[Chronic cervical vagal stimulation. Mechanisms of action and clinical relevance for heart failure]. / Chronische zervikale vagale Stimulation. Mechanismen und momentaner klinischer Stellenwert bei der Herzinsuffizienz.

Increased sympathetic nerve activity and reduced vagal activity are associated with increased mortality in patients after myocardial infarction and patients with chronic heart failure; furthermore, vagal withdrawal has been documented to precede acute decompensation. Experimental studies have indicated that increased parasympathetic activity by means of vagal stimulation may reduce mortality in animal models of postinfarction sudden cardiac death and of chronic heart failure. First clinical results have demonstrated that chronic vagus nerve stimulation in heart failure patients with severe systolic dysfunction appears to be safe and tolerable and may improve the quality of life and left ventricular (LV) function. Vagus nerve stimulation gives rise to these potential clinical benefits by multiple mechanisms of action, including reduced heart rate, restoration of heart rate variability and baroreflex sensitivity, suppression of proinflammatory cytokines and antiarrhythmic effects. First clinical results suggest that vagal nerve stimulation is safe and tolerable and could lead to a marked clinical improvement but discrepancies in the findings due to different study designs warrant further discussion.

[Baroreflex activation therapy. A novel interventional approach to treat heart failure with reduced ejection fraction]. / Baroreflexaktivierungstherapie. Ein neuer interventioneller Ansatz zur Behandlung der systolischen Herzinsuffizienz.

Sympathovagal imbalance plays an important role in the progression of heart failure with reduced ejection fraction. Baroreflex activation therapy (BAT), i. e. electrical stimulation of baroreceptors located at the carotid sinus, can reduce sympathetic and enhance parasympathetic tone. Large animal studies on BAT demonstrated improvements in cardiac function, arrhythmogenic risk and a survival benefit compared to untreated controls. The recently published Neo Randomized Heart Failure Study, the first multicenter, randomized and controlled trial of optimal medical and device therapy alone or plus BAT in patients with a left ventricular ejection fraction ≤ 35 %, demonstrated a reasonable safety profile of BAT in this severely ill patient population and no relevant interactions with other devices. The study found significant improvements in the New York Heart Association (NYHA) class of heart failure, quality of life as well as 6 min walking distance and data pointed to a reduction in hospitalization rates. Moreover, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were significantly reduced. This review gives an overview on BAT for the treatment of heart failure with reduced ejection fraction, from the rationale and animal experiments to the most recent clinical data and future perspectives.

[Rise of the machines? Left ventricular assist devices for treatment of severe heart failure]. / "Rise of the machines?" Linksventrikuläre Unterstützungssysteme zur Behandlung der schweren Herzinsuffizienz.

The use of left ventricular assist devices (LVAD) as a treatment for severe heart failure has gained momentum in recent years. Even at this stage the number of worldwide LVAD implantations far exceeds the volume of heart transplantations in view of the chronic shortage of donor organs. Third generation continuous flow assist devices have helped to improve survival, quality of life and symptom burden of heart failure patients in comparison to a regimen of optimal medication management. Alongside bridging to transplantation, destination therapy has become an established strategy of LVAD implantation. A careful patient selection process is crucial for a good clinical outcome after device implantation and risk assessment for postoperative right ventricular failure is of particular importance in this context. The rate of hospitalization during LVAD support is still high, despite the step-wise attempts to widen the indications to less severely ill heart failure patients. An effective perioperative and postoperative management will help to lower the incidence of complications (e.g. bleeding, infections, thromboembolic events and right ventricular failure) and to improve the encouraging results of mechanical circulatory support.

[Implantable hemodynamic monitoring devices]. / Implantierbare hämodynamische Monitorsysteme.

Heart failure is one of the most frequent diagnoses in hospital admissions in Germany. In the majority of these admissions acute decompensation of an already existing chronic heart failure is responsible. New mostly wireless and remote strategies for monitoring, titration, adaptation and optimization are the focus for improvement of the treatment of heart failure patients and the poor prognosis. The implantation of hemodynamic monitoring devices follows the hypothesis that significant changes in hemodynamic parameters occur before the occurrence of acute decompensation requiring readmission. Three different hemodynamic monitoring devices have so far been investigated in clinical trials employing right ventricular pressure, left atrial pressure and pulmonary artery pressure monitoring. Only one of these systems, the CardioMENS™ HF monitoring system, demonstrated a significant reduction of hospitalization due to heart failure over 6 months in the CHAMPION trial. The systematic adaptation of medication in the CHAMPION trial significantly differed from the usual care of the control arm over 6 months. This direct day to day management of diuretics is currently under intensive investigation; however, further studies demonstrating a positive effect on mortality are needed before translation of this approach into guidelines. Without this evidence a further implementation of pressure monitoring into currently used devices and justification of the substantial technical and personnel demands are not warranted.

[Cardiac contractility modulation. A new form of therapy for patients with heart failure and narrow QRS complex?]. / Kardiale Kontraktilitätsmodulation. Eine neue Therapieform für herzinsuffiziente Patienten mit schmalem Kammerkomplex?

Cardiac contractility modulation (CCM) is a stimulation therapy by an implantable impulse generator, which enhances ventricular contractile performance by delivering CCM impulses to the right ventricle during the absolute refractory period. The CCM signals mediate increased inotropy by prolonging the duration of the action potential, which leads to an enhanced influx of calcium into cardiomyocytes and a greater release of calcium by the sarcoplasmic reticulum. The increase of cardiac contractility is not associated with increased oxygen consumption. Several small studies have shown that CCM therapy can safely improve symptoms of heart failure and peak oxygen consumption in patients with moderate to severe heart failure who are not eligible for resynchronization therapy. Therefore, CCM is a novel potential therapy for patients with heart failure, an ejection fraction ≤ 35 % and a normal QRS duration < 130 ms. However, apart from selecting appropriate patients for CCM therapy there are still unanswered questions, such as the impact of CCM therapy on established clinical endpoints. At present no data are available which have shown that CCM therapy leads to reduction of hospitalization for heart failure or mortality.

Cost-effectiveness of natriuretic peptide-based screening and collaborative care: a report from the STOP-HF (St Vincent's Screening TO Prevent Heart Failure) study.

AIMS: Prevention of cardiovascular disease and heart failure (HF) in a cost-effective manner is a public health goal. This work aims to assess the cost-effectiveness of the St Vincent's Screening TO Prevent Heart Failure (STOP-HF) intervention. METHODS AND RESULTS: This is a substudy of 1054 participants with cardiovascular risk factors [median age 65.8 years, interquartile range (IQR) 57.8:72.4, with 4.3 years, IQR 3.4:5.2, follow-up]. Annual natriuretic peptide-based screening was performed, with collaborative cardiovascular care between specialist physicians and general practitioners provided to patients with BNP levels >50 pg/mL. Analysis of cost per case prevented and cost-effectiveness per quality-adjusted life year (QALY) gained was performed. The primary clinical endpoint of LV dysfunction (LVD) with or without HF was reduced in intervention patients [odds ratio (OR) 0.60; 95% confidence interval (CI) 0.38-0.94; P = 0.026]. There were 157 deaths and/or emergency hospitalizations for major adverse cardiac events (MACE) in the control group vs. 102 in the intervention group (OR 0.68; 95% CI 0.49-0.93; P = 0.01). The cost per case of LVD/HF prevented was €9683 (sensitivity range -€843 to €20 210), whereas the cost per MACE prevented was €3471 (sensitivity range -€302 to €7245). Cardiovascular hospitalization savings offset increased outpatient and primary care costs. The cost per QALY gain was €1104 and the intervention has an 88% probability of being cost-effective at a willingness to pay threshold of €30 000. CONCLUSION: Among patients with cardiovascular risk factors, natriuretic peptide-based screening and collaborative care reduced LVD, HF, and MACE, and has a high probability of being cost-effective. TRIAL REGISTRATION: NCT00921960.

Cardiac resynchronization therapy acutely improves ventricular-arterial coupling by reducing the arterial load: assessment by pressure-volume loops.

BACKGROUND: Cardiac resynchronization therapy (CRT) has been demonstrated to improve ventricular-arterial coupling by reducing effective arterial elastance (Ea) on long-term follow-up. Detailed invasive studies showing possible acute peripheral effects of CRT are not available. We evaluated the hemodynamic effects of CRT in patients with systolic dysfunction, in order to investigate the impact on ventricular-arterial coupling and, in particular, on Ea immediately after the initiation of pacing. METHODS: We studied 37 heart failure patients undergoing CRT implantation based on conventional criteria. On implantation, left ventricular (LV) pressure and volume data were determined via a conductance catheter. Twelve patients with a standard indication for electrophysiologic study and preserved LV function served as a control group. RESULTS: In comparison with the control group, heart failure patients showed reduced systolic and diastolic function. LV end-systolic elastance (Ees: end-systolic pressure/volume) was impaired (0.79 ± 0.33 mm Hg/mL vs 1.84 ± 0.89 mm Hg/mL, P = 0.012) and Ees/Ea reduced (0.36 ± 0.17 vs 1.19 ± 1.81, P = 0.022). In heart failure patients, CRT immediately improved systolic function, increasing stroke work from 3.9 ± 1.8 L*mm Hg to 6.9 ± 3.3 L*mm Hg (P < 0.001) and Ees to 1.02 ± 0.62 mm Hg/mL (P = 0.001). Ea decreased from 2.59 ± 1.35 mm Hg/mL to 1.68 ± 0.91 mm Hg/mL (P < 0.001), leading to an increase in Ees/Ea to 0.70 ± 0.38 (P < 0.001). CONCLUSION: Our data indicate that switching CRT on induces an immediate reduction in arterial load, conceivably as a consequence of restored autonomic balance.

Normalization of left ventricular ejection fraction after cardiac resynchronization therapy also normalizes survival.

BACKGROUND: Earlier studies in patients with reduced left ventricular ejection fraction (LVEF) ≤35% and prolonged QRS showed better survival outcomes with cardiac resynchronization therapy (CRT). Some patients respond dramatically to CRT by improving their LVEF to the normal range and are considered "super-responders." Our aim was to determine whether super-responders survival increases to levels comparable to the general population. We compared the survival of super-responders to the general population matched for age and sex. METHODS: Of 909 patients with CRT device implantation between September 1998 and July 2008, 814 patients had pre- and post-CRT echocardiogram. A total of 95 patients with LVEF ≥ 50% following CRT were classified as super-responders. For 92 super-responders, who had U.S. Social Security numbers, an age- and sex-matched example was selected from the Social Security Life Tables. An expected survival plot of the matched population was then compared to the actual survival of super-responders. RESULTS: Super-responders had comparable survival to the age-sex matched general population (P = 0.53), and Kaplan-Meier survival analysis in 92 patients showed that super-responders with CRT pacemakers had similar survival to those with CRT implantable cardioverter defibrillators (P = 0.77). Super-responders were more likely to be females (54% vs 25%, P < 0.001) and less likely to have significant coronary artery disease (62% vs 42%, P < 0.001). CONCLUSIONS: Normalization of LVEF by CRT improves survival to levels comparable to the general population. This observation favors the concept that some CRT candidates have a cardiomyopathy likely generated by the conduction abnormality that is reversible through biventricular pacing.

Clinical experience with low-dose continuous infusion of furosemide in acute heart failure: assessment of efficacy and safety.

INTRODUCTION: Clinical data are scarce for furosemide administered as a low-dose (<160 mg/24 hours) continuous intravenous infusion in acute heart failure (HF). Our purpose was to evaluate the efficacy and safety of low-dose continuous infusion of furosemide on diuretic response, renal function, and patient outcomes. METHODS: A retrospective study of patients with acute HF who received furosemide administered as a continuous infusion after initial therapy with intermittent boluses (usually 40-80 mg every 12 hours). End points included mean hourly urine output, incidence of acute renal injury, and outcome disparities of patients who developed acute renal injury. Comparison of patients with preserved and reduced left ventricular ejection fraction (LVEF) was also performed. RESULTS: The study included 150 patients (age 57 ± 13 years, male gender 61%, admission weight 87 ± 32 kg, LVEF 37 ± 15%, 28% preserved LVEF). Mean initial and maximum furosemide doses were 5.1 ± 1.1 mg/h and 6.2 ± 2.2 mg/h, respectively. Mean duration of therapy was 51.4 ± 67.5 hours. Continuous infusion of furosemide was associated with a significant increase in mean hourly urine output compared to baseline (150 ± 77 mL/h vs 116 ± 69 mL/h, P < .001). Acute renal injury developed in 19% of patients, with 70% of those occurring within the first 48 hours of therapy. Mean serum creatinine (baseline 1.55 ± 1.50 mg/dL vs at discharge 1.64 ± 1.61 mg/dL, P = .20) and estimated glomerular filtration rate (baseline 67 ± 39 mL/min vs at discharge 67 ± 43 mL/min, P = .89) did not significantly change over the course of the hospitalization. Development of acute renal injury was associated with poorer outcomes, higher furosemide dose, and longer duration of furosemide therapy. Diuretic response and safety were not different between patients with preserved or reduced LVEF. CONCLUSIONS: In patients with acute HF, furosemide administered as a low-dose continuous infusion was effective in achieving diuresis and was not associated with a detectable effect on renal function. This diuretic approach appeared to be similarly effective and safe in patients with preserved LVEF.

Intra- and interobserver reproducibility of left ventricular mechanical dyssynchrony assessment by real time three-dimensional echocardiography.

BACKGROUND: Real time three-dimensional (3D) echocardiography allows the assessment of left ventricular (LV) mechanical dyssynchrony and may be useful in predicting response to cardiac resynchronization therapy. However, reproducibility of 3D dyssynchrony in past reports varied widely. We evaluated intra- and interobserver reproducibility of parameters of LV mechanical dyssynchrony by 3D echocardiography and explored the impact of image quality as a possible source of variability. METHODS: LV volumes and ejection fraction (LV EF) were measured by 3D echocardiography in 90 subjects. LV mechanical dyssynchrony was calculated as the standard deviation of the time-to-minimum segmental volume (Tmsv) over 16 (SDI16) and 12 (SDI12) segments and as the maximum time-difference in Tmsv over 16 (Dif16), 12 (Dif12), and 2 (DifS-L) segments. Opposing wall delay in peak myocardial systolic velocity (S-L delay) by tissue Doppler imaging (TDI) was also evaluated. RESULTS: Feasibility of 3D measurements was 88.9%. Intra- and interobserver intraclass correlation coefficients were excellent for LV volumes, LV EF, and S-L delay (all ≥ 0.90), very good for SDI16 (0.83 and 0.85), moderate to good for SDI12, Dif16, Dif12, and DifS-L (0.51-0.81). No systematic bias was present between readings for 3D dyssynchrony, but limits of agreement resulted fairly large for most parameters with the exception of SDI16, which showed reproducibility slightly lower than TDI. Suboptimal image quality was a significant source of variability in 3D-dyssynchrony assessment. CONCLUSIONS: The 3D assessment of LV volumes and dyssynchrony was feasible in our community-based cohort. SDI16 was the most reproducible among 3D-dyssynchrony parameters and the least affected by image quality.

Magnetic resonance imaging assessment of intraventricular dyssynchrony and delayed enhancement as predictors of response to cardiac resynchronization therapy in patients with heart failure of ischaemic and non-ischaemic etiologies.

PURPOSE: To assess the value of dyssynchrony and myocardial viability assessment by cardiac magnetic resonance (CMR) in prediction of response to cardiac resynchronization therapy (CRT) in patients with heart failure (HF) of both ischaemic and non-ischaemic etiologies. MATERIALS AND METHODS: Patients scheduled for CRT in NYHA class II-IV, left ventricular ejection fraction <35%, QRS ≥ 120 ms were included. Tagged cine and late gadolinium enhancement (LGE) images were performed. Dyssynchrony was assessed with inTag toolbox and LGE was quantified using cutoff value at half of maximal signal in the scar. Cardiopulmonary exercise test, echocardiography and blood testing for NT-proBNP levels were done at baseline and 6 months after CRT. RESULTS: 52 patients (age 60.3 ± 13 years) were included. 26 patients (50%) met response criteria. The ischaemic etiology of HF was more frequent (69% vs. 31%, p=0.002), the percent of LGE was higher (7.7% [0-13.5%] vs. 19.0% (0-31.9%], p=0.013), regional vector of circumferential strain variance (RVV) was lower (0.27 ± 0.08 vs. 0.34 ± 0.09, p=0.009) and uniformity of radial strain was higher (0.72 ± 0.25 vs. 0.56 ± 0.29, p=0.046) in non-responders vs. responders. Multivariate logistic regression showed that RVV predicted response to CRT (HR 2.3, 95% CI 1.02-5.02, p=0.0430) independently of LGE and the etiology of heart failure. In the subgroup of patients with ischaemic HF the extend of transmural scar within myocardium was higher in non-responders vs. responders (26.3% vs. 15.0% respectively, p=0.01) and was a predictor of response to CRT in univariable analysis (HR 0.87, 95% CI 0.77-0.98, p=0.025) providing the sensitivity of 76% and specificity of 75% at the cutoff point of 18% in the prediction of poor response to CRT. In patients with non-ischaemic HF QRS was wider (162 ms vs. 140 ms, p=0.04), regional vector of strain variance (RVV) was higher (0.39 vs. 0.25, p=0.002) and uniformity of radial strain was lower (0.52 vs. 0.80, p=0.049) in non-responders vs. responders. Univariable logistic regression showed that RVV was a predictor of response to CRT (HR 1.50, 95% CI 1.06-2.13, p=0.022), providing the sensitivity of 94% and specificity of 85% at the cutoff point of 0.31. CONCLUSIONS: CMR derived parameters of dyssynchrony such as RVV may provide an additive value in prediction of response to CRT, especially in patients with non-ischaemic etiology of heart failure. In patients with ischaemic HF the transmurality of LGE is an important predictor of lack of response to CRT.

Valsartan plus hydrochlorothiazide: a review of its use since its introduction.

INTRODUCTION: This review focuses on the role of the fixed-dose combination (FDC) drug valsartan/hydrochlorothiazide (HCTZ) in the treatment of hypertension. Effective blood pressure control often is not achieved with monotherapy and, instead, requires combinations of drugs with different mechanisms of action to produce additive or synergistic effects. AREAS COVERED: FDC valsartan/HCTZ enhances not only efficacy for blood pressure control but also provides beneficial effects on target organs beyond that expected from arterial pressure reduction alone. Data describe key clinical trial experiences with the FDC, with particular attention to efficacy and tolerability. Literature searches of these various topics were conducted in January 2011. There is evidence of potential benefits with this combination associated with left ventricular hypertrophy, left ventricular dysfunction and renal disease. The FDC is an effective treatment for patients with hypertension and is superior to monotherapy than either drug alone. EXPERT OPINION: In addition to the benefits of each drug, valsartan/HCTZ's metabolic interactions reduce some of the negative effects of both compounds. With its increased simplicity, minimal side-effect profile and efficacy without a significant cost penalty, valsartan/HCTZ represents an excellent choice for antihypertensive therapy.

Altered left ventricular contraction pattern during right ventricular pacing: assessment using real-time three-dimensional echocardiography.

BACKGROUND: Chronic right ventricular apical (RVA) pacing has been associated with increased risk of heart failure and adverse outcome. The acute effects of RVA pacing on three-dimensional (3D) ventricular function and mechanical dyssynchrony are not well known. We performed a real-time 3D echocardiographic (RT3DE) study to assess global and regional left ventricular function during RVA pacing. METHODS: Twenty-six patients with implanted cardiac devices and normal intrinsic atrioventricular conduction were included in the study. RT3DE was performed during intrinsic sinus rhythm and during RVA pacing. Quantification of global and regional left ventricular function was performed offline by time-volume analysis of 16 myocardial segments. Time to reach minimum regional volume was calculated for each segment as a percentage of the cardiac cycle. The systolic dyssynchrony index (SDI) was defined as the standard deviation of these time periods. Longitudinal function was assessed by time-volume analysis of apical, midventricular, and basal segments. RESULTS: During RVA pacing, a reversed apical-to-basal longitudinal contraction sequence was observed in 58% of all patients. RVA pacing was associated with increased left ventricular (LV) dyssynchrony (SDI increase from 4.4 ± 2.2% to 6.3 ± 2.4%, P = 0.001) and reduced LV ejection fraction (decrease from 53 ± 13% to 47 ± 14%, P = 0.05). CONCLUSION: RT3DE assessment of LV function provides evidence that pacing from the RVA results in acute alterations in LV contraction sequence and increased LV dyssynchrony. Further studies are warranted to assess the potential of RT3DE to identify patients who might be at increased risk of pacing-induced heart failure or who might benefit from alternate-site or multisite pacing.

Assessment of cardiac function during mechanical circulatory support: the quest for a suitable clinical index.

A new index to assess left ventricular (LV) function in patients implanted with continuous flow left-ventricular assist devices (LVADs) is proposed. Derived from the pump flow signal, this index is defined as the coefficient (k) of the semilogarithmic relationship between "pseudo-ejection" fraction (pEF) and the volume discharged by the pump in diastole, (V d). pEF is defined as the ratio of the "pseudo-stroke volume" (pSV) to V d. The pseudo-stroke volume is the difference between V d and the volume discharged by the pump in systole (V s), both obtained by integrating pump flow with respect to time in a cardiac cycle. k was compared in-vivo with others two indices: the LV pressure-based index, M(TP), and the pump flow-based index, I(Q). M(TP) is the slope of the linear regression between the "triple-product" and end-diastolic pressure, EDP. The triple-product, TP = LV SP.dP/dt(max). HR, is the product of LV systolic pressure, maximum time-derivative of LV pressure, and heart rate. I(Q) is the slope of the linear regression between maximum time-derivative of pump flow, dQ/dt(max), and pump flow peak-to-peak amplitude variation, Q(P2P). To test the response of k to contractile state changes, contractility was altered through pharmacological interventions. The absolute value of k decreased from 1.354 ± 0.25 (baseline) to 0.685 ± 0.21 after esmolol infusion. The proposed index is sensitive to changes in inotropic state, and has the potential to be used clinically to assess contractile function of patients implanted with VAD.

Non-invasive assessment of myocardial contractility from force-frequency relationship in patients with implanted pacemakers: first results.

AIMS: In the normal heart, myocardial contractility is augmented at elevated heart rates. This effect is known as force-frequency relationship (FFR). The FFR is altered in failing hearts and may be used to detect myocardial function impairment. Force-frequency relationship measurements usually require invasive techniques and have therefore rarely been used in clinical practice. We studied the feasibility of FFR determination by implanted pacemakers as a non-invasive method in pacemaker patients. METHODS AND RESULTS: During follow-up visits in 30 patients with implanted pacemakers and normal heart function, the intracardiac impedance (IZ) was recorded by the pacemaker during incremental pacing at 80, 100, and 120 bpm. The time interval between the ventricular pacing pulse and IZmax (tIZm) and the maximum acceleration of the IZ change during myocardial contraction (IZacc: d2Z/dt2 max) were determined. Isovolumetric acceleration (IVA) was measured in parallel by tissue Doppler echocardiography at the right free wall, the left free wall, and the septum. With increasing pacing rates, the time interval tIZm shortened significantly and maximum acceleration IZacc increased significantly, consistent with the FFR. The best correlation was achieved between IZacc and IVA septal. CONCLUSION: Permanent pacemakers offering intracardiac IZ measurements can be used for monitoring FFR changes and, possibly, for low-effort first-line monitoring of myocardial disease.