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Aims Bi-atrial remodelling in patients with atrial fibrillation (AF) is rarely assessed and data on the presence of right atrial (RA) fibrosis, the relationship between RA and left atrial (LA) fibrosis, and possible association of RA remodelling with AF recurrence after ablation in patients with AF is limited. Methods and results A total of 110 patients with AF undergoing initial pulmonary vein isolation (PVI) were included in the present study. All patients were in sinus rhythm during cardiac magnetic resonance (CMR) imaging performed prior to ablation. LA and RA volumes and function (volumetric and feature tracking strain) were derived from cine CMR images. The extent of LA and RA fibrosis was assessed from 3D late gadolinium enhancement images. AF recurrence was followed up for 12 months after PVI using either 12-lead electrocardiograms or Holter monitoring. Arrhythmia recurrence was observed in 39 patients (36%) after the 90-day blanking period, occurring at a median of 181 (interquartile range: 122–286) days. RA remodelling parameters were not significantly different between patients with and without AF recurrence after ablation, whereas LA remodelling parameters were different (volume, emptying fraction, and strain indices). LA fibrosis had a strong correlation with RA fibrosis (r = 0.88, P < 0.001). Both LA and RA fibrosis were not different between patients with and without AF recurrence. Conclusions This study shows that RA remodelling parameters were not predictive of AF recurrence after AF ablation. Bi-atrial fibrotic remodelling is present in patients with AF and moreover, the amount of LA fibrosis had a strong correlation with the amount of RA fibrosis.

Introduction: Approximately 18% of patients with atrial fibrillation (AF) undergo a repeat ablation within 12 months after their index ablation. Despite the high prevalence, comparative studies on nonpulmonary vein (PV) target strategies in repeat AF ablation are scarce. Here, we describe 12 months efficacy of non-PV and PV target ablations as a repeat ablation strategy. Methods: A multicentre retrospective, descriptive study was conducted with data of 280 patients who underwent repeat AF ablation. The ablation strategy for repeat ablation was at the operators' discretion. Non-PV target ablation (n = 140) included PV reisolation, posterior wall isolation, mitral line, roofline, and/or complex fractionated atrial electrogram ablation. PV target ablation (n = 140), included reisolation and/or wide atrium circumferential ablation. Patients' demographics and rhythm outcomes during 12 months follow-up were analyzed. Results: At 12 months, more atrial tachyarrhythmias were observed in the non-PV target group (48.6%) compared to the PV target group (29.3%, p =.001). Similarly, a significantly higher AF and atrial tachycardia (AT) recurrence rate was observed after non-PV target ablation compared to PV target ablation (36.4% vs. 22.1% and 22.9% vs. 10.7%). After adjustment, a significantly higher risk of AT recurrence remained in the non-PV target group. Both groups significantly de-escalated antiarrhythmic drug use; de-escalation was more profound after PV target ablation. Patients with isolated PVs during non-PV target ablation had a significantly higher risk for AF recurrence than those with reconnected PVs. Conclusion: Compared to PV target ablation, non-PV target repeat ablation did not improve outcomes after 12 months and was independently associated with an increased risk for AT recurrences.

Aims Judicious patient selection for cardiac resynchronization therapy (CRT) may further enhance treatment response. Progress has been made by using improved markers of electrical dyssynchrony and mechanical discoordination, using QRSAREA, and systolic rebound stretch of the septum (SRSsept) or systolic stretch index (SSI), respectively. To date, the relation between these measurements has not yet been investigated. Methods and results A total of 240 CRT patients were prospectively enrolled from six centres. Patients underwent standard 12-lead electrocardiography, and echocardiography, at baseline, 6-month, and 12-month follow-up. QRSAREA was derived using vectorcardiography, and SRSsept and SSI were measured using strain-analysis. Reverse remodelling was measured as the relative decrease in left ventricular end-systolic volume, indexed to body surface area (ΔLVESVi). Sustained response was defined as ≥15% decrease in LVESVi, at both 6- and 12-month follow-up. QRSAREA and SRSsept were both strong, multivariable adjusted, variables associated with reverse remodelling. SRSsept was associated with response, but only in patients with QRSAREA ≥ 120 μVs (AUC = 0.727 vs. 0.443). Combined presence of SRSsept ≥ 2.5% and QRSAREA ≥ 120 μVs significantly increased reverse remodelling compared with high QRSAREA alone (ΔLVESVi 38 ± 21% vs. 22 ± 21%). As a result, 92% of left bundle branch block (LBBB)-patients with combined electrical and mechanical dysfunction were ‘sustained’ volumetric responders, as opposed to 51% with high QRSAREA alone. Conclusion Parameters of mechanical dyssynchrony are better associated with response in the presence of a clear underlying electrical substrate. Combined presence of high SRSsept and QRSAREA, but not high QRSAREA alone, ensures a sustained response after CRT in LBBB patients.

Background: A significant number of patients experience recurrent atrial fibrillation (AF) after ablation. Various risk scores have been described that may predict outcomes after AF ablation. In this study, we aimed to compare ten previously described risk scores with regard to their predictive value for post-ablation AF recurrence and procedural complications. Methods: A total of 482 AF patients (63% paroxysmal AF, 66% male, mean age 62 ± 9 years) undergoing initial radiofrequency pulmonary vein isolation (PVI) were included in the present analysis. Prior to ablation, all patients underwent both transthoracic echocardiography (TTE) and either cardiac CT imaging or CMR imaging. The following risk scores were calculated for each patient: APPLE, ATLAS, BASE-AF 2, CAAP-AF, CHADS 2, CHA 2DS 2-VASc, DR-FLASH, HATCH, LAGO and MB-LATER. Results: Median follow-up was 16 (12–31) months. AF recurrence after a 90-day blanking period was observed in 199 patients (41%), occurring after a median of 183 (124–360) days. AF recurrence was less frequent in paroxysmal AF patients compared to non-paroxysmal AF patients (34% vs. 54%, p < 0.001). Overall periprocedural complication rate was 6%. All scores, except the HATCH score, demonstrated statistically significant but poor predictive value for recurrent AF after ablation (area under curve [AUC] 0.553–0.669). CHA 2DS 2-VASc and CAAP-AF were the only risk scores with predictive value for procedural complications (AUC 0.616, p = 0.043; AUC 0.615, p = 0.044; respectively). Conclusions: Currently available risk scores perform poorly in predicting outcomes after AF ablation. These data suggest that the utility of these scores for clinical decision-making is limited.

Aims: Risk stratification models of sudden cardiac death (SCD) are based on the assumption that risk factors of SCD affect risk to a similar extent in both sexes. The aim of the study is to evaluate differences in clinical outcomes between sexes and evaluate whether risk factors associated with appropriate device therapy (ADT) differ between men and women. Methods and results: We performed a cohort study of implantable cardioverter defibrillator (ICD) patients referred for primary or secondary prevention of SCD between 2009 and 2018. Multivariable Cox regression models for prediction of ADT were constructed for men and women separately. Of 2300 included patients, 571 (25%) were women. Median follow-up was 4.6 (inter-quartile range: 4.4–4.9) years. Time to ADT was shorter for men compared with women [hazard ratio (HR) 1.71, P

Contains fulltext : 233789.pdf (Publisher’s version ) (Open Access) AIMS: In non-ischaemic dilated cardiomyopathy (DCM), concomitant right ventricular (RV) dysfunction is frequently observed. This study sought to determine the correlation of RV dysfunction with several cardiac magnetic resonance (CMR) imaging characteristics in patients with DCM, and the prognostic value of RV dysfunction on all-cause mortality and ventricular arrhythmias (VA) was evaluated. METHODS AND RESULTS: Consecutive patients with DCM and left ventricular (LV) dysfunction (ejection fraction

Aims Patient selection for cardiac resynchronization therapy (CRT) may be enhanced by evaluation of systolic myocardial stretching. We evaluate whether systolic septal rebound stretch (SRSsept) derived from speckle tracking echocardiography is a predictor of reverse remodelling after CRT and whether it holds additive predictive value over the simpler visual dyssynchrony assessment by apical rocking (ApRock). Methods and results The association between SRSsept and change in left ventricular end-systolic volume (ΔLVESV) at 6 months of follow-up was assessed in 200 patients. Subsequently, the additive predictive value of SRSsept over the assessment of ApRock was evaluated in patients with and without left bundle branch block (LBBB) according to strict criteria. SRSsept was independently associated with ΔLVESV (β 0.221, P = 0.002) after correction for sex, age, ischaemic cardiomyopathy, QRS morphology and duration, and ApRock. A high SRSsept (≥optimal cut-off value 2.4) also coincided with more volumetric responders (ΔLVESV ≥ −15%) than low SRSsept in the entire cohort (70.0% and 56.4%), in patients with strict LBBB (83.3% vs. 56.7%, P = 0.024), and non-LBBB (70.7% vs. 46.3%, P = 0.004). Moreover, in non-LBBB patients, SRSsept held additional predictive information over the assessment of ApRock alone since patients that showed ApRock and high SRSsept were more often volumetric responder than those with ApRock but low SRSsept (82.8% vs. 47.4%, P = 0.001). Conclusion SRSsept is strongly associated with CRT-induced reduction in left ventricular end-systolic volume and holds additive prognostic information over QRS morphology and ApRock. Our data suggest that CRT patient selection may be improved by assessment of SRSsept, especially in the important subgroup without strict LBBB. Clinical trial registration The MARC study was registered at clinicaltrials.gov: NCT01519908.

Background Currently, no specific treatment exists for heart failure with preserved ejection fraction (HFpEF). Left ventricular (LV) relaxation during diastole is a highly energy-demanding process, while energy homeostasis is known to be compromised in HFpEF. We hypothesise that trimetazidine – a fatty acid β‑oxidation inhibitor – improves LV diastolic function in HFpEF, by altering myocardial substrate use and improving the myocardial energy status. Objectives To assess whether trimetazidine improves LV diastolic function by improving myocardial energy metabolism in HFpEF. Methods The DoPING-HFpEF trial is a randomised, double-blind, placebo-controlled cross-over intervention trial comparing the efficacy of trimetazidine and placebo in 25 patients with stable HFpEF. The main inclusion criteria are: New York Heart Association functional class II to IV, LV ejection fraction ≥50%, and evidence of LV diastolic dysfunction. Patients are treated with one 20-mg trimetazidine tablet or placebo thrice daily (twice daily in the case of moderate renal dysfunction) for two periods of 3 months separated by a 2-week washout period. The primary endpoint is the change in pulmonary capillary wedge pressure during different intensities of exercise measured by right heart catheterisation. Our key secondary endpoint is the myocardial phosphocreatine (PCr)/ATP ratio measured by phosphorus-31 magnetic resonance spectroscopy and its relation to the primary endpoint. Exploratory endpoints are 6‑min walk distance, N-terminal pro-brain natriuretic peptide levels, and quality of life. Conclusion The DoPING-HFpEF is a phase-II trial that evaluates the effect of trimetazidine, a metabolic modulator, on diastolic function and myocardial energy status in HFpEF. [EU Clinical Trial Register: 2018-002170-52; NTR registration: NL7830]

Introduction: Radiofrequency (RF) atrial fibrillation (AF) ablation using a catheter dragging technique may shorten procedural duration and improve durability of pulmonary vein isolation (PVI) by creating uninterrupted linear ablation lesions. We compared a novel AF ablation approach guided by Grid annotation allowing for “drag lesions” with a standard point-by-point ablation approach in a single-center randomized study. Methods: Eighty-eight paroxysmal or persistent AF patients were randomized 1:1 to undergo RF-PVI with either a catheter dragging ablation technique guided by Grid annotation or point-by-point ablation guided by Ablation Index (AI) annotation. In the Grid annotation arm, ablation was visualized using 1 mm³ grid points coloring red after meeting predefined stability and contact force criteria. In the AI annotation arm, ablation lesions were created in a point-by-point fashion with AI target values set at 380 and 500 for posterior/inferior and anterior/roof segments, respectively. Patients were followed up for 12 months after PVI using ECGs, 24-h Holter monitoring and a mobile-based one-lead ECG device. Results: Procedure time was not different between the two randomization arms (Grid annotation 71 ± 19 min, AI annotation 72 ± 26 min, p =.765). RF time was significantly longer in the Grid annotation arm compared with the AI annotation arm (49 ± 8 min vs. 37 ± 8 min, respectively, p

Item does not contain fulltext OBJECTIVES: The aim of the present study was to determine the effect of a delayed versus an immediate invasive approach on final infarct size and clinical outcome up to 1 year. BACKGROUND: Up to 24% of patients with acute coronary syndromes present with ST-segment elevation myocardial infarction (STEMI) but show complete resolution of ST-segment elevation and symptoms before revascularization. Current guidelines do not clearly state whether these patients with transient STEMI should be treated with a STEMI-like or non-ST-segment elevation acute coronary syndrome-like intervention strategy. METHODS: In this multicenter trial, 142 patients with transient STEMI were randomized 1:1 to either delayed or immediate coronary intervention. Cardiac magnetic resonance imaging was performed at 4 days and at 4-month follow-up to assess infarct size and myocardial function. Clinical follow-up was performed at 4 and 12 months. RESULTS: In the delayed (22.7 h) and the immediate (0.4 h) invasive groups, final infarct size as a percentage of the left ventricle was very small (0.4% [interquartile range: 0.0% to 2.5%] vs. 0.4% [interquartile range: 0.0% to 3.5%]; p = 0.79), and left ventricular function was good (mean ejection fraction 59.3 +/- 6.5% vs. 59.9 +/- 5.4%; p = 0.63). In addition, the overall occurrence of major adverse cardiac events, consisting of death, recurrent infarction, and target lesion revascularization, up to 1 year was low and not different between both groups (5.7% vs. 4.4%, respectively; p = 1.00). CONCLUSIONS: At follow-up, patients with transient STEMI have limited infarction and well-preserved myocardial function in general, and delayed or immediate revascularization has no effect on functional outcome and clinical events up to 1 year.

Background During pulmonary vein isolation (PVI), nonisolation after initial encircling of the pulmonary veins (PVs) may be due to gaps in the initial ablation line, or alternatively, earliest PV activation may occur on the intervenous carina and ablation within the wide‐area circumferential ablation (WACA) circle is needed to eliminate residual conduction. This study investigated prognostic implications and predictors of gap‐related persistent conduction (gap‐RPC) and carina‐related persistent conduction (carina‐RPC) during PVI. Methods and Results Two hundred fourteen atrial fibrillation (AF) patients (57% paroxysmal, 61% male, mean age 62 ± 9 years) undergoing first contact force‐guided radiofrequency PVI were studied. Preprocedural cardiac computed tomography imaging was used to assess left atrial and PV anatomy. PVI was assessed directly after initial WACA circle creation, after a minimum waiting period of 30 minutes, and after adenosine infusion. Persistent conduction was targeted for additional ablation and classified as gap‐RPC or carina‐RPC, depending on the earliest activation site. The 1‐year AF recurrence rate was higher in patients with gap‐RPC (47%) compared to patients without gap‐RPC (28%; P = .003). No significant difference in 1‐year recurrence rate was found between patients with carina‐RPC (37%) and patients without carina‐RPC (31%; P = .379). Multivariate analyses identified paroxysmal AF and WACA circumference as independent predictors of gap‐RPC, whereas carina width and WACA circumference correlated with carina‐RPC. Conclusions Gap‐RPC is associated with increased AF recurrence risk after PVI, whereas carina‐RPC does not predict AF recurrence. Moreover, gap‐RPC and carina‐RPC have different correlates and may thus have different underlying mechanisms.

Aims: Various strain parameters and multiple imaging techniques are presently available including cardiovascular magnetic resonance (CMR) tagging (CMR-TAG), CMR feature tracking (CMR-FT), and speckle tracking echocardiography (STE). This study aims to compare predictive performance of different strain parameters and evaluate results per imaging technique to predict cardiac resynchronization therapy (CRT) response. Methods and results: Twenty-seven patients were prospectively enrolled and underwent CMR and echocardiographic examination before CRT implantation. Strain analysis was performed in circumferential (CMR-TAG, CMR-FT, and STE-circ) and longitudinal (STE-long) orientations. Regional strain values, parameters of dyssynchrony, and discoordination were calculated. After 12 months, CRT response was measured by the echocardiographic change in left ventricular (LV) end-systolic volume (LVESV). Twenty-six patients completed follow-up; mean LVESV change was −29 ± 27% with 17 (65%) patients showing ≥15% LVESV reduction. Measures of dyssynchrony (SD-TTPLV) and discoordination (ISFLV) were strongly related to CRT response when using CMR-TAG (R2 0.61 and R2 0.57, respectively), but showed poor correlations for CMR-FT and STE (all R2 ≤ 0.32). In contrast, the end-systolic septal strain (ESSsep) parameter showed a consistent high correlation with LVESV change for all techniques (CMR-TAG R2 0.60; CMR-FT R2 0.50; STE-circ R2 0.43; and STE-long R2 0.43). After adjustment for QRS duration and QRS morphology, ESSsep remained an independent predictor of response per technique. Conclusions: End-systolic septal strain was the only parameter with a consistent good relation to reverse remodelling after CRT, irrespective of assessment technique. In clinical practice, this measure can be obtained by any available strain imaging technique and provides predictive value on top of current guideline criteria.

Mismatch between areas of reduced myocardial blood flow (MBF) and reduced myocardial innervation (defect areas) may be used to estimate the risk for ventricular arrhythmias. The presence of a mismatch zone can be derived using a combined protocol consisting of both an MBF scan and an (11)C-meta-hydroxyephedrine ((11)C-HED) scan. The rate of influx from blood to myocardium (K1) of (11)C-HED is proportional to MBF and can potentially be used as an index for defining MBF defects. The aim of this study was to assess whether K1 derived from an (11)C-HED scan can be used as an index of MBF, potentially allowing for an assessment of MBF-innervation mismatch areas from a single (11)C-HED scan.Seventeen patients with known ischemic cardiomyopathy underwent dynamic (15)O-water and (11)C-HED scans. Discrete arterial blood samples were taken during (11)C-HED scans for metabolite correction of the image-derived input function. (11)C-HED influx rate was obtained using a single-tissue-compartment model and compared with transmural MBF (MBFT), defined as MBF as measured with (15)O-water multiplied by perfusable tissue fraction. Defect sizes were obtained from parametric K1 and MBFT images, using 50% of a remote control segment as the cutoff value.There was a significant correlation between MBFT and K1 (y = 0.40x + 0.05 mL·g(-1)·min(-1), r = 0.80, P0.001), although K1 was significantly lower than MBFT (slope of the regression line significantly different from 1, P0.001). Correlation between MBFT and K1 defect sizes was high (y = 0.89x + 1.38%, r = 0.95, P0.001), with no significant difference in mean defect size based on K1 or MBFT (20.9% ± 11.3% and 20.1% ± 10.7% for MBFT and K1, respectively, P = 0.41).(11)C-HED influx rate K1 can be used as an alternative to a separate MBF scan for assessing mismatch areas between MBF and myocardial innervation.

Chronotropic incompetence (CI) is generally defined as the inability to increase the heart rate (HR) adequately during exercise to match cardiac output to metabolic demands. In patients with heart failure (HF), however, this definition is unsuitable because metabolic demands are unmatched to cardiac output in both conditions. Moreover, HR dynamics in patients with HF differ from those in healthy subjects and may be affected by β-blocking medication. Nevertheless, it has been demonstrated that CI in HF is associated with reduced functional capacity and poor survival. During exercise, the normal heart increases both stroke volume and HR, whereas in the failing heart, contractility reserve is lost, thus rendering increases in cardiac output primarily dependent on cardioacceleration. Consequently, insufficient cardioacceleration because of CI may be considered a major limiting factor in the exercise capacity of patients with HF. Despite the profound effects of CI in this specific population, the issue has drawn limited attention during the past years and is often overlooked in clinical practice. This might partly be caused by a lack of standardized approach to diagnose the disease, further complicated by changes in HR dynamics in the HF population, which render reference values derived from a normal population invalid. Cardiac implantable electronic devices (implantable cardioverter defibrillator; cardiac resynchronization therapy) now offer a unique opportunity to study HR dynamics and provide treatment options for CI by rate-adaptive pacing using an incorporated sensor that measures physical activity. This review provides an overview of disease mechanisms, diagnostic strategies, clinical consequences, and state-of-the-art device therapy for CI in HF.

The main eligibility criterion for primary prevention implantable cardioverter defibrillator (ICD) therapy, that is, left ventricular ejection fraction (LVEF), is based on large clinical trials using primarily 2-dimensional echocardiography (2DE). Presently, cardiac magnetic resonance imaging (MRI) is considered the gold standard for LVEF assessment. It has been demonstrated that cardiac MRI assessment results in lower LVEFs compared with 2DE. Consequently, cardiac MRI-LVEF assessment may lead to more patients eligible for ICD implantation with potential clinical consequences. The aim of this study was to evaluate the clinical impact of cardiac MRI-LVEF versus 2DE-LVEF assessment for ICD eligibility. A total of 149 patients with cardiac MRI-LVEF ≤35% referred for primary prevention ICD implantation who underwent both 2DE and cardiac MRI-LVEF assessment were retrospectively included. 2DE-LVEF was computed by Simpson's biplane method. Cardiac MRI-LVEF was computed after outlining the endocardial contours in short-axis cine images. Appropriate device therapy (ADT) and all-cause mortality were evaluated during 2.9 ± 1.7 years of follow-up. The present study found that cardiac MRI-LVEF was significantly lower compared with 2DE-LVEF (23 ± 8% vs 30 ± 8%, respectively, p0.001), resulting in 29 (19%) more patients eligible for ICD implantation according to the current guidelines (LVEF ≤35%). Patients with 2DE-LVEF35% but cardiac MRI-LVEF ≤35% experienced a lower ADT rate compared with patients having 2DE-LVEF ≤35% (2.1% vs 10.4% per year, respectively, p = 0.02). Application of cardiac MRI-LVEF cutoff of 30% resulted in 119 eligible patients experiencing 9.9% per year ADT, comparable with 2DE-LVEF cut-off value of 35%. In conclusion, cardiac MRI-LVEF assessment resulted in more patients eligible for ICD implantation compared with 2DE who showed a relatively low event rate during follow-up. The event rate in patients with cardiac MRI-LVEF ≤30% was comparable with patients having a 2DE-LVEF ≤35%. This study suggests the need for re-evaluation of cardiac MRI-based LVEF cut-off values for ICD eligibility.

Aims Sympathetic denervation typically occurs in the infarcted myocardium and is associated with sudden cardiac death. Impaired innervation was also demonstrated in non-infarcted myocardium in ischaemic and dilated cardiomyopathy (ICMP and DCMP). Factors affecting sympathetic nerve integrity in remote myocardium are unknown. Perfusion abnormalities, even in the absence of epicardial coronary artery disease, may relate to sympathetic dysfunction. This study was aimed to assess the interrelations of myocardial blood flow (MBF), contractile function, and sympathetic innervation in non-infarcted remote myocardium. Methods and results Seventy patients with ICMP or DCMP and LVEF ≤35% were included. [15O]H2O- and [11C]hydroxyephedrine (HED) PET was performed to quantify resting MBF, hyperaemic MBF, and sympathetic innervation. Cardiovascular magnetic resonance (CMR) imaging was performed to assess left ventricular function, mass, wall thickening, and scar size. Wall thickening, [11C]HED retention index (RI), and MBF were assessed in remote segments without scar, selected on CMR. [11C]HED RI was correlated with resting MBF ( r = 0.41, P < 0.001) and hyperaemic MBF ( r = 0.55, P < 0.001) in remote myocardium in both ICMP and DCMP. In addition, LV volumes ( r = −0.40, P = 0.001), LV mass ( r = −0.31, P = 0.008), and wall thickening ( r = 0.45, P < 0.001) correlated with remote [11C]HED RI. Multivariable analysis revealed that hyperaemic MBF ( B = 0.79, P < 0.001), wall thickening ( B = 0.01, P = 0.03), and LVEDV ( B = −0.03, P = 0.02) were independent predictors for remote [11C]HED RI. Conclusion Hyperaemic MBF is independently associated with sympathetic innervation in non-infarcted remote myocardium in patients with ICMP and DCMP. This suggests that microvascular dysfunction might be an important factor related to sympathetic nerve integrity. Whether impaired hyperaemic MBF is the primary cause of this relation remains unclear.

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%). [ 15 O]H 2 O 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 P 75% transmurality was higher ( P 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.

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.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.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).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.

Aims 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. Methods and results Forty-one patients were analysed in the present study. During temporary biventricular pacing before implantation, acute changes in LV pump function were assessed by pressure–volume loop measurements and related to long-term response after CRT. In the study population [30 (71%) men, NYHA class 2.9 ± 0.4, EF 28 ± 7%, QRS 150 ± 25 ms], baseline mean stroke work (SW) and dP/dtmax were 4.6 ± 2.6 L ×mmHg and 874 ± 259 mmHg/s, respectively. During biventricular pacing, mean SW and dP/dtmax increased significantly by 43 ± 39% (+ 2.2 ± 2.4 L × mmHg, P < 0.001) and 13 ± 18% (+ 96 ± 136 mmHg/s, P < 0.001), respectively. In long-term responders (n = 29, 71%) compared with non-responders (n = 12, 29%), the acute increase in SW was significantly higher (+57 ±33% vs. + 10 ±30%, P < 0.001), whereas the acute increase in dP/dtmax was not significantly different between responders and non-responders (+ 15 ±18% vs. 6 ±15%, P = 0.139). Receiver operating characteristic (ROC) curve analysis indicated that SW was superior to dP/dtmax, QRS duration and LV dyssynchrony in prediction of response to CRT. A cut-off value for SW of 20% yielded a sensitivity of 90% and specificity of 75% to predict reverse remodelling at 6 months. Conclusion Invasive assessment of acute haemodynamics is a reliable tool to determine individual response to CRT. An acute increase in SW predicts long-term response to CRT with a higher accuracy than an acute increase in dP/dtmax, baseline QRS duration, and degree of LV mechanical dyssynchrony.

UNLABELLED Perfusable tissue index (PTI) is a marker of myocardial viability and requires acquisition of transmission, (15)O-CO, and (15)O-H(2)O scans. The aim of this study was to generate parametric PTI images from a (15)O-H(2)O PET/CT scan without an additional (15)O-CO scan. METHODS Data from 20 patients undergoing both (15)O-H(2)O and (15)O-CO scans were used, assessing correlation between PTI based on (15)O-CO (PTI(CO)) and on fitted blood volume fractions (PTI(Vb)). In addition, parametric PTI(Vb) images of 10 patients undergoing (15)O-H(2)O PET/CT scans were generated using basis-function methods and compared with PTI(Vb) obtained using nonlinear regression. Simulations were performed to study the effects of noise on PTI(Vb). RESULTS Correlation between PTI(CO) and PTI(Vb) was high (r(2) = 0.73). Parametric PTI(Vb) correlated well with PTI(Vb) obtained using nonlinear regression (r(2) = 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 (15)O-H(2)O PET/CT scan.

Hemodynamic optimization of Cardiac Resynchronization Therapy (CRT) with quadripolar left ventricular (LV) leads can increase CRT benefits. Most often the maximum rate of LV pressure rise (dP/dtmax) is used but stroke work (SW) incorporates both pressure and volume changes. Previously we showed SW

Multi point pacing (MPP) with a quadripolar left ventricular (LV) lead may increase response to cardiac resynchronization therapy (CRT), although factors associated with response to MPP are unknown. Heart failure patients with a left bundle branch block were analyzed during CRT implantation with a

In patients with left bundle branch block (LBBB), QRS duration (QRSd) is dependent on both myocardial conduction velocity and conduction path length. Previously, we demonstrated that normalizing QRSd to left ventricular (LV) dimension, to adjust for conduction path length, improved prediction of

Background: Intraoperative measurements of left ventricular (LV) pacing and sensing values were assessed using a novel 0.014-inch guidewire (Visionwire®, Biotronik GmbH, Berlin, Germany) enabling pacing and sensing at the distal tip before final LV lead implantation. Methods: Twenty-two consecutive patients selected for cardiac resynchronization therapy were studied. Results: Significant correlation was found between the LV pacing threshold as assessed by the Visionwire® and values after final LV lead implantation (r = 0.92, P < 0.001). Correlation for LV sensing was also significant (r = 0.72, P < 0.001). No significant correlation was present with respect to phrenic nerve stimulation. However, no phrenic nerve stimulation at 10 V/0.5 ms using the Visionwire® identified 88% of patients without phrenic nerve stimulation at 10 V/0.5 ms with subsequent LV lead measurements. Conclusion: This technique may facilitate transvenous LV lead implantation by preventing implantation in a unsuitable target vessel with respect to pacing and sensing values or phrenic nerve stimulation, thereby reducing procedure and fluoroscopy time.

Background Left ventricular segmental wall motion analysis is important for clinical decision making in cardiac diseases. Strain analysis with myocardial tissue tagging is the non-invasive gold standard for quantitative assessment, however, it is time-consuming. Cardiovascular magnetic resonance myocardial feature-tracking (CMR-FT) can rapidly perform strain analysis, because it can be employed with standard CMR cine-imaging. The aim is to validate segmental peak systolic circumferential strain (peak SCS) and time to peak systolic circumferential strain (T2P-SCS) analysed by CMR-FT against tissue tagging, and determine its intra and inter-observer variability. Methods Patients in whom both cine CMR and tissue tagging has been performed were selected. CMR-FT analysis was done using endocardial (CMR-FTendo) and mid-wall contours (CMR-FTmid). The Intra Class Correlation Coefficient (ICC) and Pearson correlation were calculated. Results 10 healthy volunteers, 10 left bundle branch block (LBBB) and 10 hypertrophic cardiomyopathy patients were selected. With CMR-FT all 480 segments were analyzable and with tissue tagging 464 segments. Significant differences in mean peak SCS values of the total study group were present between CMR-FTendo and tissue tagging (-23.8 ± 9.9% vs -13.4 ± 3.3%, p

Objective: We determined, via a bioassay, if inotropic factors are released in the coronary circulation of the rat heart and if changes in cardiac perfusion change papillary muscle inotropy. Methods: An isolated isometrically contracting rat papillary muscle ( n = 5, acceptor) was superfused with Tyrode or with reoxygenated coronary venous effluent from an isolated isovolumically beating rat heart (donor) at 27°C, which was perfused with Tyrode according to Langendorff. The superfusion solution in the muscle bath was exchanged completely in 90 s. During coronary venous effluent superfusion, the flow of the heart (donor) was changed in steps. Results: The peak force of the papillary muscle (acceptor) was unaffected by a change from Tyrode to coronary venous effluent superfusion, but time to half relaxation (RT1/2) significantly increased by 23.0 ± 9.0% (mean ± s.d.) and positive dF/dtmax significantly decreased by 14.6 ± 4.7%. These twitch characteristics were unaffected by changes in coronary perfusion while in the heart isovolumic developed left ventricular pressure did increase with perfusion (the Gregg phenomenon). Conclusions: Factors that affect papillary muscle contractility are released into the coronary circulation, but their effect is independent of the magnitude of coronary perfusion.

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 …

The effect of perfusion on diastolic muscle properties was investigated in six isolated right ventricular papillary muscles from rat hearts perfused with a crystalloid solution via the septal artery. Stress-strain relations were obtained at different perfusion pressures. Increased perfusion pressure caused an increase of stress at large strains but a decrease of stress at low strains. Thus stress-free strain increased with increasing perfusion pressure. Stress-strain relations of a given muscle at different perfusion pressures (range 12–122 cmH2O) intersected at a single “crossover” strain. Muscle stiffness, defined as the slope of the stress-strain relation, increased at all strains. Muscle diameter measurements indicated that the observed changes of the stress-strain relation occurred in association with vascular filling rather than with formation of edema. To explain the findings, the papillary muscle was modeled by two parallel compartments: muscle cells (together with the extracellular matrix) and vasculature. Perfusion was assumed to have an effect on the axial vascular properties but not on muscle cells. Combination of the stress-strain data of the muscle compartment and the vascular compartment (taken from literature) predicted stress-strain relations similar to those obtained in our perfused papillary muscles. We conclude that increased muscle stiffness at increased perfusion pressure is mainly caused by pressure-dependent changes in mechanical behavior of the vascular compartment.