Donald D. Hegland

Assessment of Myocardial Scarring Improves Risk Stratification in Patients Evaluated for Cardiac Defibrillator Implantation

OBJECTIVES We tested whether an assessment of myocardial scarring by cardiac magnetic resonance imaging (MRI) would improve risk stratification in patients evaluated for implantable cardioverter-defibrillator (ICD) implantation. BACKGROUND Current sudden cardiac death risk stratification emphasizes left ventricular ejection fraction (LVEF); however, most patients suffering sudden cardiac death have a preserved LVEF, and many with poor LVEF do not benefit from ICD prophylaxis. METHODS One hundred thirty-seven patients undergoing evaluation for possible ICD placement were prospectively enrolled and underwent cardiac MRI assessment of LVEF and scar. The pre-specified primary endpoint was death or appropriate ICD discharge for sustained ventricular tachyarrhythmia. RESULTS During a median follow-up of 24 months the primary endpoint occurred in 39 patients. Whereas the rate of adverse events steadily increased with decreasing LVEF, a sharp step-up was observed for scar size >5% of left ventricular mass (hazard ratio [HR]: 5.2; 95% confidence interval [CI]: 2.0 to 13.3). On multivariable Cox proportional hazards analysis, including LVEF and electrophysiological-study results, scar size (as a continuous variable or dichotomized at 5%) was an independent predictor of adverse outcome. Among patients with LVEF >30%, those with significant scarring (>5%) had higher risk than those with minimal or no (≤5%) scarring (HR: 6.3; 95% CI: 1.4 to 28.0). Those with LVEF >30% and significant scarring had risk similar to patients with LVEF ≤30% (p = 0.56). Among patients with LVEF ≤30%, those with significant scarring again had higher risk than those with minimal or no scarring (HR: 3.9; 95% CI: 1.2 to 13.1). Those with LVEF ≤30% and minimal scarring had risk similar to patients with LVEF >30% (p = 0.71). CONCLUSIONS Myocardial scarring detected by cardiac MRI is an independent predictor of adverse outcome in patients being considered for ICD placement. In patients with LVEF >30%, significant scarring (>5% LV) identifies a high-risk cohort similar in risk to those with LVEF ≤30%. Conversely, in patients with LVEF ≤30%, minimal or no scarring identifies a low-risk cohort similar to those with LVEF >30%.

A requirement for the rac1 GTPase in the signal transduction pathway leading to cardiac myocyte hypertrophy.

We have used adenoviral-mediated gene transfer of a constitutively active (V12rac1) and dominant negative (N17rac1) isoform of rac1 to assess the role of this small GTPase in cardiac myocyte hypertrophy. Expression of V12rac1 in neonatal cardiac myocytes results in sarcomeric reorganization and an increase in cell size that is indistinguishable from ligand-stimulated hypertrophy. In addition, V12rac1 expression leads to an increase in atrial natriuretic peptide secretion. In contrast, expression of N17rac1, but not a truncated form of Raf-1, attenuated the morphological hypertrophy associated with phenylephrine stimulation. Consistent with the observed effects on morphology, expression of V12rac1 resulted in an increase in new protein synthesis, while N17rac1 expression inhibited phenylephrine-induced leucine incorporation. These results suggest rac1 is an essential element of the signaling pathway leading to cardiac myocyte hypertrophy.

Real-Time 3-Dimensional Transesophageal Echocardiography During Left Atrial Radiofrequency Catheter Ablation for Atrial Fibrillation

Left atrial radiofrequency catheter ablation has been recognized as an important treatment option for drug-refractory symptomatic atrial fibrillation.1 Recent consensus on technique favors catheter ablation directed to the left atrium near the pulmonary vein (PV) ostium to achieve PV isolation.2 However, ablation in the region of the ligament of Marshall (LOM) to achieve electrical isolation of the left PVs can be difficult because of variable catheter stability. The superior extent of the LOM protrudes into the body of the left atrium between the anterior region of the left PV antrum and the left atrial appendage (Figure 1A). Inadvertent misdirection of ablative lesions anterior to the LOM in the region of the left atrial appendage increases the risk of cardiac perforation and does not contribute to successful PV isolation, and misdirection of ablative lesions posteriorly into the left PV or posterior left PV antrum can result in PV stenosis or fatal esophageal injury,2 respectively. Thus, circumferential isolation of the left PVs via precise delivery of ablative lesions outside the PV ostium, including the region of the LOM ridge, would be expected to enhance procedural safety and efficacy.3 More specifically, …

Clinical outcome as a function of the PR-interval— there is virtue in moderation: data from the Duke Databank for cardiovascular disease

AIMS Recently, a U-shaped association between PR-interval and the risk of developing atrial fibrillation was described, with higher risk in patients with long and short PR-intervals. Little is known regarding the association of PR-interval duration and mortality. The objective of the current study was to explore the relationship between PR-interval and major cardiovascular outcomes in patients with known coronary heart disease. METHODS AND RESULTS Patients in sinus rhythm, undergoing coronary angiography at Duke University Medical Center between 1989 and 2010, who had significant stenosis in at least one native coronary artery, were included. Patients with arrhythmia, second- or third-degree AV-block, QRS > 120 ms were excluded. A total of 9,637 patients were included (median age 63, IQR 55-71 years, 67% men). After adjustment for relevant covariates, the risk of a CV event increased with a decreasing PR-interval (10 ms decrements) for PR-interval values <162 ms (all-cause mortality; HR 1.057, 95% CI 1.019-1.096, P = 0.0030, composite of death or stroke; HR 1.047, 95% CI 1.011-1.085, P = 0.0095 and composite of cardiovascular death or cardiovascular rehospitalization; HR 1.032, 95% CI 1.002-1.063, P = 0.0387). No statistically significant changes in the risk associated with PR-interval for values >162 ms were seen for any of the studied endpoints. CONCLUSION In patients with coronary heart disease, a prolongation of the PR-interval was not independently associated with poor outcomes, but a PR-interval shorter than normal was associated with increased all-cause mortality and other major cardiovascular events.

Impact of using a telescoping-support catheter system for left ventricular lead placement on implant success and procedure time of cardiac resynchronization therapy.

Proper positioning of the left ventricular (LV) lead improves clinical outcomes and survival in patients receiving cardiac resynchronization therapy (CRT). Techniques of LV lead insertion using contrast injection and a telescoping system of delivery catheters to support advancement of the lead into the target branch may allow more efficient, targeted lead placement. We sought to evaluate the impact of an LV lead implant approach using telescoping‐support catheters (group TS) on success rate, lead location, and procedural time compared to standard over‐the‐wire implant techniques (group OTW).

Preprocedural ECG‐Gated Computed Tomography for Prevention of Complications during Lead Extraction

Preprocedural multidetector computed tomography (MDCT) may identify patients at risk for mechanical complications during lead extraction.

Effect of a dominant negative ras on myocardial hypertrophy by using adenoviral-mediated gene transfer.

BACKGROUND The small guanosine triphosphate-binding protein ras regulates a signal transduction cascade linking cell surface receptors to mitogen-activated protein kinase (MAPK). Because the molecular signaling mechanisms underlying cardiac hypertrophy remain unclear, the current study examined the regulatory role of ras in both the biochemical and morphologic aspects of hypertrophy. METHODS Adenoviral-mediated gene transfer was used to express a dominant negative mutant of ras (rasN17) at high efficiency in primary neonatal ventricular myocytes. Beta-galactosidase staining and Western blot analysis confirmed successful transfection and expression of the rasN17 gene product. MAPK activity was measured by an in vitro kinase assay resulting in radioactive phosphorus labeled product. Morphologic hypertrophy was assessed by fluorescein-conjugated phalloidin. RESULTS Compared with uninfected or control adenoviral-infected cells, myocytes infected with rasN17 demonstrated attenuated basal MAPK activity. In contrast, rasN17 expression did not affect endothelin 1-induced MAPK activation. Morphologic studies showed that although rasN17 produced a phenotypic difference in the basal state, the ability of cardiac myocytes to morphologically respond to endothelin 1 stimulation, as manifested by sarcomeric reorganization, remained unaltered by the expression of the rasN17 gene product. CONCLUSIONS Endothelin 1-stimulated MAPK activation and endothelin 1-induced morphologic hypertrophy are ras-independent processes.

Outcomes Associated With Extraction Versus Capping and Abandoning Pacing and Defibrillator Leads

Background: Lead management is an increasingly important aspect of care in patients with cardiac implantable electronic devices; however, relatively little is known about long-term outcomes after capping and abandoning leads. Methods: Using the 5% Medicare sample, we identified patients with de novo cardiac implantable electronic device implantations between January 1, 2000, and December 31, 2013, and with a subsequent lead addition or extraction ≥12 months after the de novo implantation. Patients who underwent extraction for infection were excluded. Using multivariable Cox proportional hazards models, we compared cumulative incidence of all-cause mortality, device-related infection, device revision, and lead extraction at 1 and 5 years for the extraction versus the cap and abandon group. Results: Among 6859 patients, 1113 (16.2%) underwent extraction, whereas 5746 (83.8%) underwent capping and abandonment. Extraction patients tended to be younger (median, 78 versus 79 years; P<0.0001), were less likely to be male (65% versus 68%; P=0.05), and had shorter lead dwell time (median, 3.0 versus 4.0 years; P<0.0001) and fewer comorbidities. Over a median follow-up of 2.4 years (25th, 75th percentiles, 1.0, 4.3 years), the overall 1-year and 5-year cumulative incidence of mortality was 13.5% (95% confidence interval [CI], 12.7–14.4) and 54.3% (95% CI, 52.8–55.8), respectively. Extraction was associated with a lower risk of device infection at 5 years relative to capping (adjusted hazard ratio, 0.78; 95% CI, 0.62–0.97; P=0.027). There was no association between extraction and mortality, lead revision, or lead extraction at 5 years. Conclusions: Elective lead extraction for noninfectious indications had similar long-term survival to that for capping and abandoning leads in a Medicare population. However, extraction was associated with lower risk of device infections at 5 years.

An Automated Surveillance Strategy to Identify Infectious Complications After Cardiac Implantable Electronic Device Procedures.

Background.  The optimum approach for infectious complication surveillance for cardiac implantable electronic device (CIED) procedures is unclear. We created an automated surveillance tool for infectious complications after CIED procedures. Methods.  Adults having CIED procedures between January 1, 2005 and December 31, 2011 at Duke University Hospital were identified retrospectively using International Classification of Diseases, 9th revision (ICD-9) procedure codes. Potential infections were identified with combinations of ICD-9 diagnosis codes and microbiology data for 365 days postprocedure. All microbiology-identified and a subset of ICD-9 code-identified possible cases, as well as a subset of procedures without microbiology or ICD-9 codes, were reviewed. Test performance characteristics for specific queries were calculated. Results.  Overall, 6097 patients had 7137 procedures. Of these, 1686 procedures with potential infectious complications were identified: 174 by both ICD-9 code and microbiology, 14 only by microbiology, and 1498 only by ICD-9 criteria. We reviewed 558 potential cases, including all 188 microbiology-identified cases, 250 randomly selected ICD-9 cases, and 120 with neither. Overall, 65 unique infections were identified, including 5 of 250 reviewed cases identified only by ICD-9 codes. Queries that included microbiology data and ICD-9 code 996.61 had good overall test performance, with sensitivities of approximately 90% and specificities of approximately 80%. Queries with ICD-9 codes alone had poor specificity. Extrapolation of reviewed infectious rates to nonreviewed cases yields an estimated rate of infection of 1.3%. Conclusions.  Electronic queries with combinations of ICD-9 codes and microbiologic data can be created and have good test performance characteristics for identifying likely infectious complications of CIED procedures.

Pulmonary Vein Contraction Before and After Radiofrequency Ablation for Atrial Fibrillation

Pulmonary Vein Contraction After Ablation. Introduction: Cardiovascular magnetic resonance imaging (cMRI) may provide a noninvasive method to test for pulmonary vein (PV) isolation after ablation for atrial fibrillation (AF) by detecting changes in PV contraction.