Cardiac imaging in heart failure in the personalized medicine era: Pathway to knowledge or Tiresias' paradox?

Tiresias was the blind prophet of Apollo in Thebes. Tiresias is a symbolic figure, which embodies a paradox: he is blind in the physical sense, but his knowledge surpasses all, as opposed to Oedipus who cannot see despite having a good eyesight. Cardiac imaging can be considered the technological extension of human eyes, which has clearly revolutionised the diagnostic approach in Cardiology and specifically in heart failure. Echocardiography contributed to an approach focused on the ejection fraction (EF) which is the cornerstone of the most recent classifications of heart failure. The recent advances in cardiac imaging raised our ability to understand the aetiological roots of disease. However, the increasing amount of information generated by the plethora of diagnostic imaging techniques raises the challenge of clinical significance. The explosion of "big data" in cardiac imaging may also impact on classifications and nomenclature and on our ability to cluster and categorize, an exercise that is becoming remarkably challenging when the quest for the particular is taken to the extreme and the infinitesimal. The essence of cardiac conditions causing heart failure would probably not entirely captured by an approach only focused on the direct visualization of the heart. Delivery of personalized medicine would not be based only on cardiac imaging, but through an holistic approach which overcomes the mere assessment of empiric reality as it appears to our eyes through the lens of increasingly advanced diagnostic techniques.

Economic evaluation of a dedicated cardiac resynchronisation therapy preassessment clinic.

INTRODUCTION: Patient evaluation before cardiac resynchronisation therapy (CRT) remains heterogeneous across centres and it is suspected a proportion of patients with unfavourable characteristics proceed to implantation. We developed a unique CRT preassessment clinic (CRT PAC) to act as a final review for patients already considered for CRT. We hypothesised that this clinic would identify some patients unsuitable for CRT through updated investigations and review. The purpose of this analysis was to determine whether the CRT PAC led to savings for the National Health Service (NHS). METHODS: A decision tree model was made to evaluate two clinical pathways; (1) standard of care where all patients initially seen in an outpatient cardiology clinic proceeded directly to CRT and (2) management of patients in CRT PAC. RESULTS: 244 patients were reviewed in the CRT PAC; 184 patients were eligible to proceed directly for implantation and 48 patients did not meet consensus guidelines for CRT so were not implanted. Following CRT, 82.4% of patients had improvement in their clinical composite score and 57.7% had reduction in left ventricular end-systolic volume ≥15%. Using the decision tree model, by reviewing patients in the CRT PAC, the total savings for the NHS was £966 880. Taking into consideration the additional cost of the clinic and by applying this model structure throughout the NHS, the potential savings could be as much as £39 million. CONCLUSIONS: CRT PAC appropriately selects patients and leads to substantial savings for the NHS. Adopting this clinic across the NHS has the potential to save £39 million.

Left ventricular epicardial electrograms show divergent changes in action potential duration in responders and nonresponders to cardiac resynchronization therapy.

BACKGROUND: A consistent feature of electrophysiological remodeling in heart failure is ventricular action potential duration (APD) prolongation. However, the effect of reverse remodeling on APD during cardiac resynchronization therapy (CRT) has not been determined in these patients. We hypothesized (1) that CRT may alter APD and (2) that the effect of CRT on APD may be different in patients who exhibit a good hemodynamic response to CRT compared with those with a poor response. METHODS AND RESULTS: Left ventricular (LV) activation recovery intervals, as a surrogate for APD, were measured from the LV epicardium in 13 patients at day 0, 6 weeks, and 6 months after CRT implant. Responders to CRT were defined as those demonstrating a ≥15% reduction in LV end-systolic volume at 6 months. The responder group had a significant reduction in LV activation recovery interval (mean, -13±12 ms; median, -16 ms; interquartile range, -2 to -19 ms) during right ventricular pacing at 6 months (P<0.05). Conversely, the nonresponders showed a significant increase in activation recovery interval (mean, +22 ms±16; median, 17 ms; interquartile range, 8 to 35 ms; P<0.05). One patient in each group was on amiodarone. CONCLUSIONS: In patients with heart failure, LV epicardial APD (activation recovery interval) altered during CRT. The effect on APD was opposite in patients showing a good hemodynamic response compared with nonresponders. The findings may provide an explanation for the persistent high incidence of arrhythmias in some patients with CRT and the additional mortality benefit observed in responders of CRT.

Benefits of endocardial and multisite pacing are dependent on the type of left ventricular electric activation pattern and presence of ischemic heart disease: insights from electroanatomic mapping.

BACKGROUND: There is considerable heterogeneity in the myocardial substrate of patients undergoing cardiac resynchronization therapy (CRT), in particular in the etiology of heart failure and in the location of conduction block within the heart. This may account for variability in response to CRT. New approaches, including endocardial and multisite left ventricular (LV) stimulation, may improve CRT response. We sought to evaluate these approaches using noncontact mapping to understand the underlying mechanisms. METHODS AND RESULTS: Ten patients (8 men and 2 women; mean [SD] age 63 [12] years; LV ejection fraction 246%; QRS duration 161 [24] ms) fulfilling conventional CRT criteria underwent an electrophysiological study, with assessment of acute hemodynamic response to conventional CRT as well as LV endocardial and multisite pacing. LV activation pattern was assessed using noncontact mapping. LV endocardial pacing gave a superior acute hemodynamic response compared with conventional CRT (26% versus 37% increase in LV dP/dt(max), respectively; P<0.0005). There was a trend toward further incremental benefit from multisite LV stimulation, although this did not reach statistical significance (P=0.08). The majority (71%) of patients with nonischemic heart failure etiology or functional block responded to conventional CRT, whereas those with myocardial scar or absence of functional block often required endocardial or multisite pacing to achieve CRT response. CONCLUSIONS: Endocardial or multisite pacing may be required in certain subsets of patients undergoing CRT. Patients with ischemic cardiomyopathy and those with narrower QRS, in particular, may stand to benefit.

A simultaneous X-Ray/MRI and noncontact mapping study of the acute hemodynamic effect of left ventricular endocardial and epicardial cardiac resynchronization therapy in humans.

BACKGROUND: Cardiac resynchronization therapy (CRT) using endocardial left ventricular (LV) pacing may be superior to conventional CRT. We studied the acute hemodynamic response to conventional CRT and LV pacing from different endocardial sites using a combined cardiac MRI and LV noncontact mapping (NCM) protocol to gain insights into the underlying mechanisms. METHODS AND RESULTS: Fifteen patients (age, 63 ± 10 years; 12 men) awaiting CRT were studied in a combined x-ray and MRI laboratory. Delayed-enhancement cardiac magnetic resonance was performed to define areas of myocardial fibrosis. Patients underwent an electrophysiological study incorporating endocardial and epicardial LV pacing. Acute hemodynamic response was measured using a pressure wire within the LV cavity to derive LV dP/dt max. NCM was used to define areas of slow conduction. There was a significant improvement in all LV pacing modes versus baseline (P<0.001). LV endocardial CRT from the best endocardial site was superior to conventional CRT, with a 79.8 ± 49.0% versus 59.6 ± 49.5% increase in LV dP/dt max of from baseline (P<0.05). The hemodynamic benefits of pacing were greater when LV stimulation was performed outside of areas of slow conduction defined by NCM (P<0.001). Delayed-enhancement cardiac magnetic resonance was able to delineate zones of slow conduction seen with NCM in ischemic patients but was unreliable in nonischemic patients. CONCLUSIONS: Endocardial LV pacing appears superior to conventional CRT, although the optimal site varies between subjects and is influenced by pacing within areas of slow conduction. Delayed-enhancement cardiac magnetic resonance was a poor predictor of zones of slow conduction in nonischemic patients.