Provision of magnetic resonance imaging for patients with 'MR-conditional' cardiac implantable electronic devices: an unmet clinical need.

AIMS: Increasing need for magnetic resonance imaging (MRI) has driven the development of MR-conditional cardiac implantable electronic devices (CIEDs; pacemakers and defibrillators); however, patients still report difficulties obtaining scans. We sought to establish current provision for MRI scanning of patients with CIEDs in England. METHODS AND RESULTS: A survey was distributed to all hospitals in England with MRI, to assess current practice. Information requested included whether hospitals currently offer MRI to this patient group, the number and type of scans acquired, local safety considerations, complications experienced and perceived obstacles to service provision in those departments not currently offering it. Responses were received from 195 of 227 (86%) of hospitals surveyed. Although 98% of departments were aware of MR-conditional devices, only 46% (n = 89) currently offer MRI scans to patients with CIED's; of these, 85% of departments perform ≤10 scans per year. No major complications were reported from MRI scanning in patients with MR-conditional devices. Current barriers to service expansion include perceived concerns regarding potential risk, lack of training, logistical difficulties, and lack of cardiology support. CONCLUSION: Provision of MRI for patients with CIEDs is currently poor, despite increasing numbers of patients with MR-conditional devices and extremely low reported complication rates.

Glucagon-like peptide-1 protects against ischemic left ventricular dysfunction during hyperglycemia in patients with coronary artery disease and type 2 diabetes mellitus.

BACKGROUND: Enhancement of myocardial glucose uptake may reduce fatty acid oxidation and improve tolerance to ischemia. Hyperglycemia, in association with hyperinsulinemia, stimulates this metabolic change but may have deleterious effects on left ventricular (LV) function. The incretin hormone, glucagon-like peptide-1 (GLP-1), also has favorable cardiovascular effects, and has emerged as an alternative method of altering myocardial substrate utilization. In patients with coronary artery disease (CAD), we investigated: (1) the effect of a hyperinsulinemic hyperglycemic clamp (HHC) on myocardial performance during dobutamine stress echocardiography (DSE), and (2) whether an infusion of GLP-1(7-36) at the time of HHC protects against ischemic LV dysfunction during DSE in patients with type 2 diabetes mellitus (T2DM). METHODS: In study 1, twelve patients underwent two DSEs with tissue Doppler imaging (TDI)-one during the steady-state phase of a HHC. In study 2, ten patients with T2DM underwent two DSEs with TDI during the steady-state phase of a HHC. GLP-1(7-36) was infused intravenously at 1.2 pmol/kg/min during one of the scans. In both studies, global LV function was assessed by ejection fraction and mitral annular systolic velocity, and regional wall LV function was assessed using peak systolic velocity, strain and strain rate from 12 paired non-apical segments. RESULTS: In study 1, the HHC (compared with control) increased glucose (13.0 ± 1.9 versus 4.8 ± 0.5 mmol/l, p < 0.0001) and insulin (1,212 ± 514 versus 114 ± 47 pmol/l, p = 0.01) concentrations, and reduced FFA levels (249 ± 175 versus 1,001 ± 333 µmol/l, p < 0.0001), but had no net effect on either global or regional LV function. In study 2, GLP-1 enhanced both global (ejection fraction, 77.5 ± 5.0 versus 71.3 ± 4.3%, p = 0.004) and regional (peak systolic strain -18.1 ± 6.6 versus -15.5 ± 5.4%, p < 0.0001) myocardial performance at peak stress and at 30 min recovery. These effects were predominantly driven by a reduction in contractile dysfunction in regions subject to demand ischemia. CONCLUSIONS: In patients with CAD, hyperinsulinemic hyperglycemia has a neutral effect on LV function during DSE. However, GLP-1 at the time of hyperglycemia improves myocardial tolerance to demand ischemia in patients with T2DM. TRIAL REGISTRATION: http://www.isrctn.org . Unique identifier ISRCTN69686930.

Utility of speckle tracking echocardiography to characterize dysfunctional myocardium in patients with ischemic cardiomyopathy referred for cardiac resynchronization therapy.

BACKGROUND: Assessment of transmural scar at the site of latest mechanical activation is relevant to maximize outcomes in cardiac resynchronization therapy (CRT). Few studies have assessed the ability of speckle tracking echocardiography (STE)-derived short-axis strain to identify segmental myocardial scar, defined by contrast-enhanced cardiac magnetic resonance imaging (CMR), in patients referred for CRT. METHODS: A total of 26 patients with ischemic cardiomyopathy who underwent preprocedure echocardiography and CMR were studied. Extent of transmural scar was assessed using contrast-enhanced CMR and corresponding peak segmental radial and circumferential strains were derived using two-dimensional (2D) STE. Total left ventricle (LV) scar volume was compared with parameters of global strain. CRT response was defined as >15% reduction in LV end systolic volume (LVESV) at 6 months. RESULTS: Speckle tracking short-axis strain analysis was technically possible in over 90% of LV segments. Applying a segmental radial strain cutoff value of 10% distinguished segments with >50% scar area with a high negative predictive value (98%). Global longitudinal strain <-5% predicted CRT response. CONCLUSIONS: Two-dimensional STE offers potential to characterize dysfunctional myocardium and define segmental scar offering an integrated imaging approach to guide LV lead placement for CRT.

Effects of Acute GLP-1 Infusion on Pulmonary and Systemic Hemodynamics in Patients With Heart Failure: A Pilot Study.

PURPOSE: Cardiovascular-safety studies assessing glucagon-like peptide (GLP)-1 receptor agonists and dipeptidyl peptidase 4 inhibitors have provided inconsistent data on the risk for developing heart failure. Animal studies have shown that GLP-1 is a vasodilator; if confirmed in humans, this may ameliorate heart failure symptoms. METHODS: In a single-center, observational pilot study, we recruited 10 patients with advanced heart failure undergoing right heart catheterization, and we recorded pulmonary hemodynamic measures, including cardiac output calculated by thermodilution and the indirect Fick method before and after a 15-minute continuous infusion of native GLP-1 (7-36) NH2. FINDINGS: There was a neutral effect of GLP-1 on all pressure and hemodynamics indices as derived by cardiac output calculated by thermodilution. However, there was a small but consistent reduction in cardiac output as calculated by the indirect Fick method after GLP-1 infusion (baseline, 4.0 [1.1] L/min vs GLP-1, 3.6 [0.9] L/min; P = 0.003), driven by a consistent reduction in mixed venous oxygen saturation after GLP-1 infusion (baseline, 62.2% [7.0%] vs GLP-1, 59.3% [6.8%]; P < 0.001), whereas arterial saturation remained constant (baseline, 96.8% [3.3%] vs GLP-1, 97.0% [3.2%]; P = 0.34). This resulted in an increase in systemic vascular resistance by Fick (baseline, 1285 [228] dyn · s/cm5 vs GLP-1, 1562 [247] dyn · s/cm5; P = 0.001). IMPLICATIONS: Acute infusion of GLP-1 has a neutral hemodynamic effect, when assessed by thermodilution, in patients with heart failure. However, GLP-1 reduces mixed venous oxygen saturation. ClinicalTrials.gov identifier: NCT02129179.

Atrial function as a guide to timing of intervention in mitral valve prolapse with mitral regurgitation.

OBJECTIVES: The purpose of this study was to determine the clinical utility of left atrial (LA) functional indexes in patients with mitral valve prolapse (MVP) and mitral regurgitation (MR). BACKGROUND: Timing of surgery for MVP remains challenging. We hypothesized that assessment of LA function may provide diagnostic utility in these patients. METHODS: We studied 192 consecutive patients in sinus rhythm with MVP, classified into 3 groups: moderate or less MR (MOD group, n = 54); severe MR without surgical indication (SEV group, n = 52); and severe MR with ≥1 surgical indication (SURG group, n = 86). Comparison was made with 50 control patients. Using 2D speckle imaging, average peak contractile, conduit, and reservoir atrial strain was recorded. Using Simpson's method we recorded maximal left atrial volume (LAVmax) and minimal left atrial volume (LAVmin), from which the total left atrial emptying fraction (TLAEF) was derived: (LAVmax-LAVmin)/LAVmax × 100%. RESULTS: TLAEF was similar in the MOD and control groups (61% vs. 57%; p = NS), was reduced in the SEV group (55%; p < 0.001 vs. control group), and markedly lower in the SURG group (40%; p < 0.001 vs. other groups). Reservoir strain demonstrated a similar pattern. Contractile strain was similarly reduced in the MOD and SEV groups (MOD 15%; SEV 14%; p = NS; both p < 0.05 vs. control group 20%) and further reduced in the SURG group (8%; p < 0.001 vs. other groups). By multivariate analysis, TLAEF (odds ratio [OR]: 0.78; p < 0.001), reservoir strain (OR: 0.91; p = 0.028), and contractile strain (OR: 0.86; p = 0.021) were independent predictors of severe MR requiring surgery. Using receiver-operating characteristic analysis, TLAEF <50% demonstrated 91% sensitivity and 92% specificity for predicting MVP with surgical indication (area under the curve: 0.96; p < 0.001). CONCLUSIONS: We report the changes in left atrial function in humans with MVP and the relationship of LA dysfunction to clinical indications for mitral valve surgery. We propose that the findings support the utility of quantitative assessment of atrial function by echocardiography as an additional tool to guide the optimum timing of surgery for MVP.

Development of a multiparametric score to predict left ventricular remodelling and prognosis after cardiac resynchronization therapy.

AIMS: Optimal delivery of CRT requires appropriate patient selection and device implantation. Echocardiographic predictors of CRT response individually appear to enhance patient selection, but do not fully reflect the complex underlying myocardial dysfunction. We hypothesized that a multiparametric approach would offer greater predictive value and sought to derive a score incorporating baseline characteristics including: dyssynchrony, LV function, and LV lead position. METHODS AND RESULTS: Data were analysed from 294 patients undergoing CRT between June 2008 and December 2012. All patients were in sinus rhythm with QRS >120 ms, NYHA class II-IV, and LVEF <35%. Detailed clinical assessment including echocardiography was completed at baseline and 6 months after CRT. Response was defined as a ≥15% reduction in LV end-systolic volume. Dyssynchrony (interventricular delay and radial strain delay), global longitudinal strain, and LV lead position were independent predictors of LV remodelling and were used to derive a predictive score which correlated with reduction in LV volume (r = - 0.5, P < 0.001) and was higher with QRS >150 ms and non-ischaemic aetiology. A cut-off score <0.6 offered the highest specificity and positive predictive value (100%) to determine non-response. A score >3.28 offered high specificity (specificity 86%, sensitivity 70%) to predict response. Survival proportion at longer term follow-up was low (21%) in the group with predictive score <0.6. CONCLUSION: A multiparametric strategy, which defines anticipated probability of response to CRT, offers potential to predict non-responders with poor long-term survival following CRT. The value of this approach in avoiding unnecessary device implantation with potential for harm requires validation in large multicentre studies.

Prognostic benefit of optimum left ventricular lead position in cardiac resynchronization therapy: follow-up of the TARGET Study Cohort (Targeted Left Ventricular Lead Placement to guide Cardiac Resynchronization Therapy).

OBJECTIVES: This study was conducted to assess the impact of left ventricular (LV) lead position on longer-term survival after cardiac resynchronization therapy (CRT). BACKGROUND: An optimal LV lead position in CRT is associated with improved clinical outcome. A strategy of speckle-tracking echocardiography can be used to guide the implanter to the site of latest activation and away from segments of low strain amplitude (scar). Long-term, prospective survival data according to LV lead position in CRT are limited. METHODS: Data from a follow-up registry of 250 consecutive patients receiving CRT between June 2008 and July 2010 were studied. The study population comprised patients recruited to the derivation group and the subsequent TARGET (Targeted Left Ventricular Lead Placement to guide Cardiac Resynchronization Therapy) randomized, controlled trial. Final LV lead position was described, in relation to the pacing site determined by pre-procedure speckle-tracking echocardiography, as optimal (concordant/adjacent) or suboptimal (remote). All-cause mortality was recorded at follow-up. RESULTS: An optimal LV lead position (n = 202) conferred LV remodeling response superior to that of a suboptimal lead position (change in LV end-systolic volume: -24 ± 15% vs. -12 ± 17% [p < 0.001]; change in ejection fraction: +7 ± 8% vs. +4 ± 7% [p = 0.02]). During long-term follow-up (median: 39 months; range: <1 to 61 months), an optimal LV lead position was associated with improved survival (log-rank p = 0.003). A suboptimal LV lead placement independently predicted all-cause mortality (hazard ratio: 1.8; p = 0.024). CONCLUSIONS: An optimal LV lead position at the site of latest mechanical activation, avoiding low strain amplitude (scar), was associated with superior CRT response and improved survival that persisted during follow-up.

Chronic dipeptidyl peptidase-4 inhibition with sitagliptin is associated with sustained protection against ischemic left ventricular dysfunction in a pilot study of patients with type 2 diabetes mellitus and coronary artery disease.

BACKGROUND: The incretin hormone, glucagon-like peptide-1, promotes myocardial glucose uptake and may improve myocardial tolerance to ischemia. Endogenous glucagon-like peptide-1 (7-36) is augmented by pharmacological inhibition of dipeptidyl peptidase-4. We investigated whether chronic dipeptidyl peptidase-4 inhibition by sitagliptin protected against ischemic left ventricular dysfunction during dobutamine stress in patients with type 2 diabetes mellitus and coronary artery disease. METHODS AND RESULTS: A total of 19 patients with type 2 diabetes mellitus underwent dobutamine stress echocardiography with tissue Doppler imaging on 2 separate occasions: the first (control) while receiving oral hypoglycemic agents, and the second after the addition of sitagliptin (100 mg once daily) for ≈4 weeks. Sitagliptin increased plasma glucagon-like peptide-1 (7-36) levels and, at peak stress, enhanced both global (ejection fraction, 70.5±7.0 versus 65.7±8.0%; P<0.0001; mitral annular systolic velocity, 11.7±2.6 versus 10.9±2.3 cm/s; P=0.01) and regional left ventricular function, assessed by peak systolic velocity and strain rate in 12 paired, nonapical segments. This was predominantly because of a cardioprotective effect on ischemic segments (strain rate in ischemic segments, -2.27±0.65 versus -1.98±0.58 s(-1); P=0.001), whereas no effect was seen in nonischemic segments (-2.19±0.48 versus -2.18±0.54 s(-1); P=0.87). At 30 minutes recovery, dipeptidyl peptidase-4 inhibition mitigated the postischemic stunning seen in the control scan. CONCLUSIONS: The addition of dipeptidyl peptidase-4 inhibitor therapy with sitagliptin to the treatment regime of patients with type 2 diabetes mellitus and coronary artery disease is associated with a sustained improvement in myocardial performance during dobutamine stress and a reduction in postischemic stunning. CLINICAL TRIAL REGISTRATION: URL: http://www.isrctn.org. Unique identifier ISRCTN61646154.

Radial strain delay based on segmental timing and strain amplitude predicts left ventricular reverse remodeling and survival after cardiac resynchronization therapy.

BACKGROUND: Dyssynchrony assessment based on the timing of regional contraction is inherently independent of underlying myocardial contractility. We tested the hypothesis that patient selection for cardiac resynchronization therapy (CRT) would be enhanced using a parameter derived from the net radial strain delay (RSD) for the 12 basal and mid-left ventricular segments (calculated radial strain delay RSD [RSDc]), based on not only timing but also amplitude of segmental strain. METHODS AND RESULTS: Echocardiographic data were analyzed in 240 patients with symptomatic heart failure undergoing CRT (New York Heart Association class III/IV; QRS >120 milliseconds; ejection fraction, 23±7%). RSDc was calculated as the sum of difference between peak radial strain and radial strain at aortic valve closure before CRT implantation. CRT response was defined as >15% reduction in left ventricular end-systolic volume at 6 months. In a derivation group (n=102), RSDc was higher in responders compared with nonresponders (74±39% versus 29±15%; P<0.001) and related to the change in left ventricular end-systolic volume (r=-0.53; P<0.001). RSDc >40% predicted remodeling (sensitivity, 87%; specificity, 88%). In the validation group (n=108), RSDc similarly predicted response (sensitivity, 89%; specificity, 84%). Survival at long-term follow-up was greater in patients with RSDc >40% (P<0.0001). CONCLUSIONS: RSDc, based on both the timing and the amplitude of segmental strain, has a strong predictive value for CRT remodeling response and long-term survival.

Optimizing benefit from CRT: role of speckle tracking echocardiography, the importance of LV lead position and scar.

Cardiac resynchronization therapy is demonstrated to be effective in patients with advanced heart failure. Correcting mechanical dyssynchrony is proposed as the predominant mechanism of response. Achieving optimum left ventricular lead position, at the site of maximal mechanical dyssynchrony but away from transmural scar, is identified as one of the main determinants of both symptomatic and prognostic benefit. Strategies employing multimodality cardiac imaging techniques have been used to identify this optimal pacing site, in addition to any potential anatomical limitations to successful implantation. Speckle tracking echocardiography offers prospective lead targeting, incorporating pathophysiological determinants of cardiac resynchronization therapy response. This review considers the key factors in defining optimum left ventricular lead location, emphasizing the role of myocardial scar. The use of speckle tracking echocardiography and the potential for this technique to be incorporated into routine practice to guide the implant strategy in an individual patient is discussed.

Cardiac protection via metabolic modulation: an emerging role for incretin-based therapies?

Cardiovascular disease continues to be a major cause of morbidity and mortality in patients with Type 2 Diabetes Mellitus. Whilst a focus on improved glucose control and HbA1c has led to a reduction in the progression and development of microvascular complications, the potential for this strategy to reduce cardiovascular event rates is less clearly defined. Identification of the incretin axis has facilitated the development of several novel therapeutic agents which target glucagon-like peptide-1 (GLP-1) pathways. The effects on glucose homeostasis are now established, but there is also now an increasing body of evidence to support a number of pleiotropic effects on the heart that may have the potential to influence cardiovascular outcomes. In this article, we review myocardial energy metabolism with particular emphasis on the potential benefits associated with a shift towards increased glucose utilisation and present the pre-clinical and clinical evidence regarding incretin effects on the heart. In addition we discuss the potential mechanism of action and benefit of drugs that modulate GLP-1 in patients with type 2 diabetes mellitus and coronary artery disease.

Patent foramen ovale: anatomy, outcomes, and closure.

Patent foramen ovale (PFO) is a normal fetal communication between the right and left atria that persists after birth. PFO is a common finding that occurs in 20-34% of the population, although its prevalence decreases with age. In most cases, a PFO poses no threat to health. However, some PFOs have the ability to open widely under certain hemodynamic conditions, which enables any bloodborne material, such as thrombi, air, or vasoactive substances, to pass from the venous to the arterial circulation, with the potential to cause a cerebrovascular event. PFO has been linked to several conditions, including cryptogenic stroke, migraine with aura, decompression illness, and systemic arterial embolism. However, the data that support PFO closure in these conditions are mostly from nonrandomized cohort series, and are often contradictory. In this Review, we discuss the existing data on PFO closure, including results of the first randomized, controlled trial comparing device closure of PFO with medical therapy for cryptogenic stroke, and we examine controversies in the literature as well as ongoing studies. We also focus on the anatomy of a PFO and how it impacts on the procedure of PFO closure with a percutaneous device.