Cornelis P. Allaart

Myocardial Energetics and Efficiency Current Status of the Noninvasive Approach

The heart is an aerobic organ that relies almost exclusively on the aerobic oxidation of substrates for generation of energy. Consequently, there is close coupling between myocardial oxygen consumption (MVo2) and the main determinants of systolic function: heart rate, contractile state, and wall stress.1 As in any mechanical pump, only part of the energy invested is converted to external power. In the case of the heart, the ratio of useful energy produced (ie, stroke work [SW]) to oxygen consumed is defined as mechanical efficiency, as originally proposed by Bing et al.2 Under normal conditions this ratio is ≈25%, and the residual energy mainly dissipates as heat.3 In pathophysiological disease states, such as heart failure, mechanical efficiency is reduced, and it has been hypothesized that the increased energy expenditure relative to work contributes to progression of the disease.4,5 Moreover, therapeutic interventions that enhance mechanical efficiency have proven to be beneficial with respect to outcome.6 It is therefore desirable to quantify efficiency of the heart to study disease processes and monitor interventions. Both cardiac oxidative metabolism and mechanical work, and thus efficiency, can be quantified through invasive measurements. Although these measurements are accurate and currently considered the gold standard, in clinical practice they are limited because of the need for dual-sided heart catheterization and selective catheterization of the coronary sinus. Recent advances in imaging techniques, however, offer the possibility to noninvasively estimate MVo2 and mechanical work by positron emission tomography and echocardiography or by magnetic resonance imaging, respectively. This review discusses the principles of mechanical efficiency, together with its invasive and noninvasive assessment, as well as their strengths and pitfalls. Finally, results from clinical pathophysiological studies are discussed. To calculate the efficiency of the heart, input and output energy must be obtained. The …

Right ventricular pacing improves right heart function in experimental pulmonary arterial hypertension: a study in the isolated heart

Right heart failure in pulmonary arterial hypertension (PH) is associated with mechanical ventricular dyssynchrony, which leads to impaired right ventricular (RV) function and, by adverse diastolic interaction, to impaired left ventricular (LV) function as well. However, therapies aiming to restore synchrony by pacing are currently not available. In this proof-of-principle study, we determined the acute effects of RV pacing on ventricular dyssynchrony in PH. Chronic PH with right heart failure was induced in rats by injection of monocrotaline (80 mg/kg). To validate for PH-related ventricular dyssynchrony, rats (6 PH, 6 controls) were examined by cardiac magnetic resonance imaging (9.4 T), 23 days after monocrotaline or sham injection. In a second group (10 PH, 4 controls), the effects of RV pacing were studied in detail, using Langendorff-perfused heart preparations. In PH, septum bulging was observed, coinciding with a reversal of the transseptal pressure gradient, as observed in clinical PH. RV pacing improved RV systolic function, compared with unpaced condition (maximal first derivative of RV pressure: +8.5 + or - 1.3%, P < 0.001). In addition, RV pacing markedly decreased the pressure-time integral of the transseptal pressure gradient when RV pressure exceeds LV pressure, an index of adverse diastolic interaction (-24 + or - 9%, P < 0.01), and RV pacing was able to resynchronize time of RV and LV peak pressure (unpaced: 9.8 + or - 1.2 ms vs. paced: 1.7 + or - 2.0 ms, P < 0.001). Finally, RV pacing had no detrimental effects on LV function or coronary perfusion, and no LV preexcitation occurred. Taken together, we demonstrate that, in experimental PH, RV pacing improves RV function and diminishes adverse diastolic interaction. These findings provide a strong rationale for further in vivo explorations.

Mechanical dyssynchrony or myocardial shortening as MRI predictor of response to biventricular pacing

To investigate whether mechanical dyssynchrony (regional timing differences) or heterogeneity (regional strain differences) in myocardial function should be used to predict the response to cardiac resynchronization therapy (CRT).

Doppler-Derived Intracoronary Physiology Indices Predict the Occurrence of Microvascular Injury and Microvascular Perfusion Deficits After Angiographically Successful Primary Percutaneous Coronary Intervention

Background—A total of 40% to 50% of patients with ST-segment–elevation myocardial infarction develop microvascular injury (MVI) despite angiographically successful primary percutaneous coronary intervention (PCI). We investigated whether hyperemic microvascular resistance (HMR) immediately after angiographically successful PCI predicts MVI at cardiovascular magnetic resonance and reduced myocardial blood flow at positron emission tomography (PET). Methods and Results—Sixty patients with ST-segment–elevation myocardial infarction were included in this prospective study. Immediately after successful PCI, intracoronary pressure–flow measurements were performed and analyzed off-line to calculate HMR and indices derived from the pressure–velocity loops, including pressure at zero flow. Cardiovascular magnetic resonance and H215O PET imaging were performed 4 to 6 days after PCI. Using cardiovascular magnetic resonance, MVI was defined as a subendocardial recess of myocardium with low signal intensity within a gadolinium-enhanced area. Myocardial perfusion was quantified using H215O PET. Reference HMR values were obtained in 16 stable patients undergoing coronary angiography. Complete data sets were available in 48 patients of which 24 developed MVI. Adequate pressure–velocity loops were obtained in 29 patients. HMR in the culprit artery in patients with MVI was significantly higher than in patients without MVI (MVI, 3.33±1.50 mm Hg/cm per second versus no MVI, 2.41±1.26 mm Hg/cm per second; P=0.03). MVI was associated with higher pressure at zero flow (45.68±13.16 versus 32.01±14.98 mm Hg; P=0.015). Multivariable analysis showed HMR to independently predict MVI (P=0.04). The optimal cutoff value for HMR was 2.5 mm Hg/cm per second. High HMR was associated with decreased myocardial blood flow on PET (myocardial perfusion reserve <2.0, 3.18±1.42 mm Hg/cm per second versus myocardial perfusion reserve ≥2.0, 2.24±1.19 mm Hg/cm per second; P=0.04). Conclusions—Doppler-flow–derived physiological indices of coronary resistance (HMR) and extravascular compression (pressure at zero flow) obtained immediately after successful primary PCI predict MVI and decreased PET myocardial blood flow. Clinical Trial Registration—URL: http://www.trialregister.nl. Unique identifier: NTR3164.

Prediction of long-term outcome of cardiac resynchronization therapy by acute pressure-volume loop measurements.

Invasive assessment of acute haemodynamic response to biventricular pacing has been proposed as a tool to determine individual response and to optimize the effects of CRT. However, the long‐term results of this approach have been poorly studied. The present study relates acute haemodynamic effects of CRT to long‐term outcome.

Parametric Images of Myocardial Viability Using a Single 15O-H2O PET/CT Scan

Perfusable tissue index (PTI) is a marker of myocardial viability and requires acquisition of transmission, 15O-CO, and 15O-H2O scans. The aim of this study was to generate parametric PTI images from a 15O-H2O PET/CT scan without an additional 15O-CO scan. Methods: Data from 20 patients undergoing both 15O-H2O and 15O-CO scans were used, assessing correlation between PTI based on 15O-CO (PTICO) and on fitted blood volume fractions (PTIVb). In addition, parametric PTIVb images of 10 patients undergoing 15O-H2O PET/CT scans were generated using basis-function methods and compared with PTIVb obtained using nonlinear regression. Simulations were performed to study the effects of noise on PTIVb. Results: Correlation between PTICO and PTIVb was high (r2 = 0.73). Parametric PTIVb correlated well with PTIVb obtained using nonlinear regression (r2 = 0.91). Simulations showed low sensitivity to noise (coefficient of variation < 10% at 20% noise). Conclusion: Parametric PTI images can be generated from a single 15O-H2O PET/CT scan.

Bisoprolol in idiopathic pulmonary arterial hypertension: an explorative study.

While beta-blockers are considered contraindicated in pulmonary arterial hypertension (PAH), the prognostic significance of sympathetic nervous system over-activity suggests a potential benefit of beta-blocker therapy. The aim of this randomised, placebo-controlled, crossover, single centre study was to determine the effects of bisoprolol on right ventricular ejection fraction (RVEF) in idiopathic PAH (iPAH) patients. Additional efficacy and safety parameters were explored. Patients with optimally treated, stable iPAH (New York Heart Association functional class II/III) were randomised to placebo or bisoprolol. Imaging and functional measurements were performed at baseline, crossover and end of study. 18 iPAH patients were included, because inclusion faltered before enrolment of the targeted 25 patients. 17 patients completed 6 months of bisoprolol, 15 tolerated bisoprolol, one patient required intravenous diuretics. Bisoprolol was associated with a lower heart rate (17 beats per minute, p=0.0001) but RVEF remained unchanged. A drop in cardiac index (0.5 L·min−1·m−2, p=0.015) was observed, along with a trend towards a decreased 6-min walking distance (6MWD). Although careful up-titration of bisoprolol was tolerated by most patients and resulted in a decreased heart rate, no benefit of bisoprolol in iPAH was demonstrated. Decreases in cardiac index and 6MWD suggest a deteriorated cardiac function. The results do not favour the use of bisoprolol in iPAH patients. A bisoprolol dose that significantly reduced heart rate was not associated with a significant change in RVEF in PAH http://ow.ly/j5D0300OgGz

Loss of opposite left ventricular basal and apical rotation predicts acute response to cardiac resynchronization therapy and is associated with long-term reversed remodeling

BACKGROUND Normal left ventricular (LV) torsion is caused by opposite basal and apical rotation. Opposite rotation can be lost in heart failure, but might be restored by pacing; therefore, the predictive value of the loss of opposite base-apex rotation in heart failure patients for the response to cardiac resynchronization therapy (CRT) was studied. METHODS AND RESULTS In 34 CRT candidates and 12 controls, basal and apical LV rotations were calculated using magnetic resonance image tagging. Loss of opposite rotation was quantified by the correlation between both rotation curves: a negative correlation indicates normal, opposite rotation and a positive correlation indicates that base and apex rotate in the same direction. In patients, LV pressure was measured invasively during biventricular stimulation. Acute response to CRT was defined by >10% increase in dP/dt(max) relative to baseline. LV volume was determined at baseline and 8 months follow-up using echocardiography. The base-apex rotation correlation (BARC) was significantly higher in acute responders (n=22) than in nonresponders (n=12) and controls (0.64+/-0.51, -0.23+/-0.67, and -0.68+/-0.22, respectively; P=.001). The sensitivity and specificity for prediction of acute response were 82% and 83%, respectively, at a cutoff value of 0.5. At follow-up, volumes could be analyzed in 18 patients. In the group with BARC >0.5, end-diastolic volume decreased by 7% (NS), end-systolic volume by 16%, and ejection fraction increased by 28% (both P=.02), whereas in the group with BARC <0.5, no significant changes were observed. CONCLUSIONS The loss of opposite base-apex rotation in patients eligible for CRT is an excellent predictor of acute response and is associated with LV reverse remodeling.

Scar tissue–guided left ventricular lead placement for cardiac resynchronization therapy in patients with ischemic cardiomyopathy: An acute pressure-volume loop study

BACKGROUND Response to cardiac resynchronization therapy (CRT) is hampered by the extent and location of left ventricular (LV) scar tissue. It is commonly advised to avoid scar tissue while placing the LV lead. However, whether individual patients benefit from this strategy remains unclear. METHODS Thirty-two CRT candidates with ischemic cardiomyopathy were enrolled from 2 successive clinical trials (TBS and E-pot study). Magnetic resonance imaging with late contrast enhancement was performed to assess location, degree and transmurality of LV scar tissue. Patients underwent invasive pressure-volume loop measurements to assess acute LV pump function changes during pacing at posterolateral (PL) and anterolateral LV sites. RESULTS In the study population (26 [81%] men, ejection fraction [EF] 22% ± 8%, QRS 149 ± 20 milliseconds), baseline mean stroke work (SW) and dP/dtmax were 4.4 ± 2.2 L∙mmHg and 849 ± 212 mmHg/s, respectively. The extent of scar tissue was inversely related to the acute increase in SW during pacing (R = -0.53, P = .002). Stimulating PL scar tissue resulted in deterioration of pump function (∆SW -17% ± 17%, P = .018), whereas pacing PL viable tissue led to an increase in pump function (∆SW +62% ± 51%, P < .001). Switching from pacing at the location of scar tissue, irrespective of the scar location, to viable tissue showed a significant increase in SW (-8% ± 20% vs +20 ± 40, P = .004). CONCLUSIONS The extent of LV scar tissue is inversely related to acute pump function improvement during CRT. Pacing at the location of (transmural) scar tissue at any site of the LV will generally deteriorate LV pump function. Placing the LV lead over viable myocardium significantly improves pump function as compared with pacing at the location of scar tissue in patients with ischemic cardiomyopathy.

Impaired Hyperemic Myocardial Blood Flow Is Associated With Inducibility of Ventricular Arrhythmia in Ischemic Cardiomyopathy

Background—Risk stratification for ventricular arrhythmias (VAs) is important to refine selection criteria for primary prevention implantable cardioverter defibrillator therapy. Impaired hyperemic myocardial blood flow (MBF) is associated with increased mortality rate in ischemic and nonischemic cardiomyopathy, which may be attributed to electric instability inducing VAs. The aim of this pilot study was to assess whether hyperemic MBF impairment may be related with VA inducibility in patients with ischemic cardiomyopathy. Methods and Results—Thirty patients with ischemic cardiomyopathy referred for primary prevention implantable cardioverter defibrillator implantation were prospectively included (26 men; 65±8 years old; left ventricular ejection fraction, 29±6%). [15O]H2O positron-emission tomography was performed to quantify resting MBF, hyperemic MBF, and coronary flow reserve. Left ventricular dimensions, function, and scar burden were assessed with cardiovascular magnetic resonance imaging. An electrophysiological study was performed to test VA inducibility. Positive electrophysiological study patients (n=12) showed reduced hyperemic MBF (1.25±0.30 versus 1.66±0.38 mL·min−1·g−1; P<0.01) and coronary flow reserve (1.59±0.49 versus 2.12±0.48; P<0.01) compared with electrophysiological study negative patients (n=18). In electrophysiological study positive patients, the number of scar segments >75% transmurality was higher (P<0.05), although scar size and border zone did not differ. Receiver-operating characteristic curve analysis indicated that impaired hyperemic MBF (area under the curve, 0.84; 95% confidence intervals [0.69–0.99]) and coronary flow reserve (area under the curve, 0.77; 95% confidence intervals [0.57–0.96]) were associated with VA inducibility. Conclusions—In this pilot study, impaired hyperemic MBF and coronary flow reserve were associated with VA inducibility in patients with ischemic cardiomyopathy. These results are hypothesis generating for a potential role of quantitative positron-emission tomography perfusion imaging in risk stratification for VAs.