Babak Nazer

Diffuse fibrosis leads to a decrease in unipolar voltage: Validation in a swine model of premature ventricular contraction-induced cardiomyopathy.

BACKGROUND Frequent premature ventricular contractions (PVCs) may lead to dilated cardiomyopathy. A leftward shift in the unipolar voltage distribution in patients with cardiomyopathy has also been described and attributed to increased fibrosis. OBJECTIVES We established a swine model of PVC-induced cardiomyopathy and assessed (1) whether an increase in left ventricular fibrosis occurs and (2) whether increased fibrosis leads to a leftward shift in the unipolar voltage distribution. METHODS Ten swine underwent implantation of ventricular pacemakers; 6 programmed to deliver a 50% PVC burden and 4 controls without pacing. Voltage maps were acquired at baseline and after 14 weeks of ventricular bigeminy. RESULTS In the PVC group, left ventricular ejection fraction decreased from 67% ± 7% to 44% ± 15% (P < .05) with no change in controls (71% ± 6% to 73% ± 4%; P = .56). The fifth percentile of the bipolar and unipolar voltage distribution at baseline was 1.63 and 5.36 mV, respectively. In the control group, after 14 weeks of pacing there was no significant change in % bipolar voltage <1.5 mV (pre 1.2% vs post 2.2%; P = .34) or % unipolar voltage <5.5 mV (pre 4.0% vs post 3.5%; P = .20). In the PVC group, there was a significant increase in % unipolar voltage <5.5 mV (5.4% vs 12.6%; P < .01), with a leftward shift in the unipolar voltage distribution. Histologically, % fibrosis was increased in the PVC group (control 1.8% ± 1.3% vs PVC 3.4% ± 2.6%; P < .01). CONCLUSION PVC-induced cardiomyopathy in swine leads to an increase in interstitial fibrosis and a leftward shift in the unipolar voltage distribution. These findings are consistent with findings in humans with PVC-induced cardiomyopathy.

Loss-of-Function KCNE2 Variants: True Monogenic Culprits of Long-QT Syndrome or Proarrhythmic Variants Requiring Secondary Provocation?

Background— Insight into type 6 long-QT syndrome (LQT6), stemming from mutations in the KCNE2-encoded voltage-gated channel &bgr;-subunit, is limited. We sought to further characterize its clinical phenotype. Methods and Results— Individuals with reported pathogenic KCNE2 mutations identified during arrhythmia evaluation were collected from inherited arrhythmia clinics and the Rochester long-QT syndrome (LQTS) registry. Previously reported LQT6 cases were identified through a search of the MEDLINE database. Clinical features were assessed, while reported KCNE2 mutations were evaluated for genotype–phenotype segregation and classified according to the contemporary American College of Medical Genetics guidelines. Twenty-seven probands possessed reported pathogenic KCNE2 mutations, while a MEDLINE search identified 17 additional LQT6 cases providing clinical and genetic data. Sixteen probands had normal resting QTc values and only developed QT prolongation and malignant arrhythmias after exposure to QT-prolonging stressors, 10 had other LQTS pathogenic mutations, and 10 did not have an LQTS phenotype. Although the remaining 8 subjects had an LQTS phenotype, evidence suggested that the KCNE2 variant was not the underlying culprit. The collective frequency of KCNE2 variants implicated in LQT6 in the Exome Aggregation Consortium database was 1.4%, in comparison with a 0.0005% estimated clinical prevalence for LQT6. Conclusions— On the basis of clinical phenotype, the high allelic frequencies of LQT6 mutations in the Exome Aggregation Consortium database, and absence of previous documentation of genotype–phenotype segregation, our findings suggest that many KCNE2 variants, and perhaps all, have been erroneously designated as LQTS-causative mutations. Instead, KCNE2 variants may confer proarrhythmic susceptibility when provoked by additional environmental/acquired or genetic factors, or both.

Therapeutic Ultrasound Promotes Reperfusion and Angiogenesis in a Rat Model of Peripheral Arterial Disease

BACKGROUND Shock wave therapy (SWT) is an acoustic technology clinically used for the non-invasive treatment of ischemic heart disease (IHD). Therapeutic ultrasound (TUS) has more recently been developed for the same indication, although its effects on reperfusion and angiogenesis have yet to be directly compared to those of SWT. METHODSANDRESULTS TUS and SWT acoustic parameters were matched, and their ability to promote angiogenesis and reperfusion in a rat hindlimb ischemia model was compared. After left femoral artery excision, 3-weekly TUS, SWT or sham treatments (n=10 rats each) of the left hindlimb were performed for 2 weeks. Laser Doppler perfusion imaging demonstrated improved perfusion with TUS (66±4% L:R hindlimb perfusion, mean±SEM, P=0.02), but not with SWT (59±4%, P=0.13) compared with sham (50±4%). Immunohistochemistry of CD31 demonstrated increased microvascular density with TUS (222.6 vessels/high-power field, P=0.001) and SWT (216.9, P=0.01) compared to sham-treated rats (196.0). Tissue vascular endothelial growth factor mRNA levels were elevated in the left hindlimb of TUS-, but not SWT- or sham-treated rats. CONCLUSIONS Direct comparison demonstrates that TUS is more effective than SWT at promoting reperfusion, whereas both therapies promote angiogenesis in ischemic gastrocnemius muscle. These results suggest that TUS may be more effective than SWT for the treatment of IHD and peripheral arterial disease.

Cardiovascular applications of therapeutic ultrasound

Ultrasound (US) has gained widespread use in diagnostic cardiovascular applications. At amplitudes and frequencies typical of diagnostic use, its biomechanical effects on tissue are largely negligible. However, these parameters can be altered to harness US’s thermal and non-thermal effects for therapeutic indications. High-intensity focused ultrasound (HIFU) and extracorporeal shock wave therapy (ECWT) are two therapeutic US modalities which have been investigated for treating cardiac arrhythmias and ischemic heart disease, respectively. Here, we review the biomechanical effects of HIFU and ECWT, their potential therapeutic mechanisms, and pre-clinical and clinical studies demonstrating their efficacy and safety limitations. Furthermore, we discuss other potential clinical applications of therapeutic US and areas in which future research is needed.

Current Treatment Strategies for Heart Failure: Role of Device Therapy and LV Reconstruction

Opinion statementMedical care of heart failure (HF) begins with the determination of the cause of the heart failure and diagnosing potential reversible causes (i.e., coronary heart disease, hyperthyroidism, etc.). Medical therapy includes pharmacological and nonpharmacological strategies that limit and/or reverse the signs and symptoms of HF. Initial behavior modification includes dietary sodium and fluid restriction to avoid weight gain; and encouraging physical activity when appropriate. Optimization of medical therapy is the first line of treatment that includes the use of diuretics, vasodilators (i.e., ACE inhibitors or ARBs), beta blockers, and potentially inotropic agents and anticoagulation depending on the patient’s severity of heart failure and LV dysfunction. As heart failure advances despite optimized medical management, cardiac resynchronization therapy (CRT), and implantable cardioverter defibrillators (ICDs) are appropriate device therapies. The development of progressive end-stage HF, despite maximal medical therapy, necessitates the consideration of mechanical circulatory devices such as ventricular assist devices (VADs) either as a bridge to heart transplantation or as destination therapy. Despite the advances in the treatment of heart failure, there is still a large morbidity and mortality associated with HF, thus the need to develop newer strategies for the treatment of HF.

Importance of Ventricular Tachycardia Induction and Mapping for Patients Referred for Epicardial Ablation

Many nonischemic cardiomyopathy (NICMP) patients referred for catheter ablation of ventricular tachycardia (VT) undergo an initial epicardial approach under general anesthesia (GA). However, GA may suppress inducibility and decrease tolerance of induced VT, leaving substrate modification as the sole ablation method.

Simultaneous thrombotic culprit lesions in two separate coronary arteries in a patient with ST-elevation myocardial infarction

A 78-year-old male with no history of coronary artery disease presented to our emergency department with intermittent chest pain that had worsened over 5 days. Electrocardiogram showed ST elevation in V1 and V2 ( Panel A ). The patient was taken emergently to the cardiac catheterization laboratory, where he developed hypotension and bradycardia requiring …

Feasibility of Rapid Linear-Endocardial and Epicardial Ventricular Ablation Using an Irrigated Multipolar Radiofrequency Ablation Catheter

Background— A common strategy for ablation of scar-based ventricular tachycardia is delivering multiple lesions in a linear pattern. Methods and Results— We tested the efficacy of a novel linear irrigated multipolar ablation catheter capable of creating linear lesions with a single application. Healthy swine underwent endocardial and epicardial linear ablation using a novel linear irrigated ablation catheter; control animals underwent focal lesions in a linear pattern over 3.5 cm with an irrigated radiofrequency catheter. The linear catheter contained 7 irrigated electrodes spaced over 3.5 cm and could deliver ⩽25 W to each electrode. Linear ablation required significantly less radiofrequency time than focal ablation (56±11 versus 497±110 seconds; P<0.0001). At gross pathology, linear (n=18) epicardial lines were longer than focal (n=8) epicardial lines (3.3±0.7 versus 2.1±0.9 cm; P<0.0005), with greater volume (3.8±2.9 versus 1.5±1.6 cm3; P=0.002). There was no difference between linear (n=22) and focal (n=7) endocardial line length or volume. Gaps (length 2.8±0.9 mm) were present in 53% of focal lines and 0% of linear ablation lines. No perforations, steam pops, or thrombus were noted. Conclusions— Compared with sequential focal radiofrequency ablation in a linear pattern, an irrigated multipolar linear ablation catheter safely delivers contiguous endocardial or epicardial lesions without gaps in a single ablation. This catheter shows promise for decreasing ventricular tachycardia ablation procedure time and improving outcome.

Epicardial Catheter Ablation Using High-Intensity Ultrasound Validation in a Swine Model

Background—Epicardial radiofrequency catheter ablation of ventricular tachycardia remains challenging because of the presence of deep myocardial scar and adjacent cardiac structures, such as the coronary arteries, phrenic nerve, and epicardial fat that limit delivery of radiofrequency energy. High-intensity ultrasound (HIU) is an acoustic energy source able to deliver deep lesions through fat, while sparing superficial structures. We developed and tested an epicardial HIU ablation catheter in a closed chest, in vivo swine model. Methods and Results—The HIU catheter is an internally cooled, 14-French, side-facing catheter, integrated with A-mode ultrasound guidance. Swine underwent percutaneous subxyphoid epicardial access and ablation with HIU (n=10 swine) at 15, 20, and 30 W. Compared with irrigated radiofrequency lesions in control swine (n = 5), HIU demonstrated increased lesion depth (HIU 11.6±3.2 mm versus radiofrequency 4.7±1.6 mm; mean±SD) and epicardial sparing (HIU 2.9±2.1 mm versus radiofrequency 0.1±0.2 mm) at all HIU powers, and increased lesion volume at HIU 20 and 30 W (P<0.0001 for all comparisons). HIU ablation over coronary arteries and surrounding epicardial fat resulted in deep lesions with normal angiographic flow. Histological disruption of coronary adventitia, but not media or intima, was noted in 44% of lesions. Conclusions—Compared with radiofrequency, HIU ablation in vivo demonstrates significantly deeper and larger lesions with greater epicardial sparing in a dose-dependent manner. Further development of this catheter may lead to a promising alternative to epicardial radiofrequency ablation.

Catheter ablation of ventricular tachycardia in patients with post-infarction cardiomyopathy

Monomorphic ventricular tachycardia (VT) in patients with post-infarction cardiomyopathy (CMP) is caused by reentry through slowly conducting tissue with in areas of myocardial scar. The use of implantable cardioverter-defibrillators (ICDs) has helped to decrease the risk of arrhythmic death in patients with post-infarction CMP, but the symptomatic and psychological burden of ICD shocks remains significant. Experience with catheter ablation has progressed substantially in the past 20 years, and is now routinely used to treat patients with post-infarction CMP who experience VT or receive ICD therapy. Depending on the hemodynamic tolerance of VT, a variety of mapping techniques may be used to identify sites for catheter ablation, including activation and entrainment mapping for mappable VTs, or substrate mapping for unmappable VTs. In this review, we discuss the pathophysiology of VT in post-infarction CMP patients, and the contemporary practice of catheter ablation.