Beating aortic valve replacement surgery as an alternative to transcatheter aortic valve implantation in a patient with severe aortic stenosis and left ventricular dysfunction.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is the standard treatment for high-risk patients with aortic stenosis (AS); however, alternative treatments for patients who are ineligible for TAVI are controversial. CASE PRESENTATION: 56 year-old female who required 6 γ dobutamine support due to congestive heart failure was diagnosed as severe aortic stenosis with bicuspid valve. Echocardiography revealed left ventricular ejection fraction (LVEF) was 15%. The patient was relatively young for TAVI, and TAVI was not licensed for patient presenting with a bicuspid aortic valve in places other than the limited institutions in Japan. On pump beating aortic valve replacement (AVR) was performed with selective antegrade coronary artery blood perfusion. She resumed a completely normal lifestyle by 3 weeks after the operation. CONCLUSIONS: A relatively young patient for TAVI who was diagnosed as aortic stenosis with severely reduced ejection fraction and bicuspid valve is reported. Beating AVR with a continuously selective antegrade-perfusion was achieved safely with good clinical results in a patient with severely reduced left ventricular (LV) function. Beating AVR can be considered as a potential alternative for patients who are ineligible for conventional surgical aortic valve replacement (SAVR) and TAVI.

Prevalence and Electrocardiographic and Electrophysiological Characteristics of Idiopathic Ventricular Arrhythmias Originating From Intramural Foci in the Left Ventricular Outflow Tract.

BACKGROUNDS: Idiopathic ventricular arrhythmias (VAs) originating from the left ventricular outflow tract (LVOT) sometimes require catheter ablation from both the endocardial and epicardial sides for their elimination, suggesting the presence of intramural VA foci. This study investigated the prevalence and electrocardiographic and electrophysiological characteristics of these idiopathic intramural LVOT VAs when compared with the idiopathic endocardial and epicardial LVOT VAs. METHODS AND RESULTS: We studied 82 consecutive VAs with origins in the aortomitral continuity (n=30), LV summit (n=34), and intramural site (n=18). The maximum deflection index (the time to the maximum deflection in the precordial leads/QRS duration) was the largest in LV summit VAs (0.52±0.07), smallest in aortomitral continuity VAs (0.45±0.06), and midrange in intramural VAs (0.49±0.05). The electrocardiographic and electrophysiological characteristics of the intramural LVOT VAs were similar to those of the aortomitral continuity VAs. The intramural LVOT VAs exhibited a significantly smaller R-wave amplitude ratio in leads III to II, and ratio of the Q-wave amplitude in leads aVL to aVR, and a significantly earlier and later local ventricular activation time relative to the QRS onset at the His bundle and successful ablation sites than the LV summit VAs, respectively. CONCLUSIONS: Intramural sites account for a significant proportion of LVOT VAs. The electrocardiographic and electrophysiological characteristics of the idiopathic intramural LVOT VAs were midrange between those of the idiopathic endocardial and epicardial LVOT VAs, and more similar to those of the idiopathic endocardial LVOT VAs than those of the idiopathic epicardial LVOT VAs.

Association between High Endocardial Unipolar Voltage and Improved Left Ventricular Function in Patients with Ischemic Cardiomyopathy.

We know that endocardial mapping reports left ventricular electrical activity (voltage) and that these data can predict outcomes in patients undergoing traditional revascularization. Because the mapping data from experimental models have also been linked with myocardial viability, we hypothesized an association between increased unipolar voltage in patients undergoing intramyocardial injections and their subsequent improvement in left ventricular performance. For this exploratory analysis, we evaluated 86 patients with left ventricular dysfunction, heart-failure symptoms, possible angina, and no revascularization options, who were undergoing endocardial mapping. Fifty-seven patients received bone marrow mononuclear cell (BMC) injections and 29 patients received cell-free injections of a placebo. The average mapping site voltage was 9.7 ± 2 mV, and sites with voltage of ≥6.9 mV were engaged by needle and injected (with BMC or placebo). For all patients, at 6 months, left ventricular ejection fraction (LVEF) improved, and after covariate adjustment this improvement was best predicted by injection-site voltage. For every 2-mV increase in baseline voltage, we detected a 1.3 increase in absolute LVEF units for all patients (P=0.038). Multiple linear regression analyses confirmed that voltage and the CD34(+) count present in bone marrow (but not treatment assignment) were associated with improved LVEF (P=0.03 and P=0.014, respectively). In an exploratory analysis, higher endocardial voltage and bone marrow CD34(+) levels were associated with improved left ventricular function among ischemic cardiomyopathy patients. Intramyocardial needle injections, possibly through stimulation of angiogenesis, might serve as a future therapy in patients with reduced left ventricular function and warrants investigation.

Blood transfusion after on-pump coronary artery bypass grafting: focus on modifiable risk factors.

OBJECTIVES: Perioperative transfusions are known to increase morbidity and mortality after coronary artery bypass grafting (CABG). The aims of the study were (1) to identify the clinical profile of the patient subset at highest risk from transfusion and (2) to disclose causative relationship and dose-dependency of transfusion on hospital mortality. METHODS: A prospective observational design was employed on a cohort of 1047 consecutive patients (median age 63.2 ± 9.3, 18.8% female, 30.6% diabetics, 31.9% urgent/emergent, 15.3% with low preoperative left ventricular ejection fraction (LVEF)) who underwent on-pump isolated CABG between January 2004 and December 2007. Univariate and multivariate regression analysis and post-hoc risk stratification, by means of propensity scoring and binary segmentation, were adopted. RESULTS: The following independent risk factors were identified: age, body surface area (BSA), preoperative glomerular filtration rate, preoperative haemoglobin, surgical priority, length of cardiopulmonary bypass, intraoperative haemodilution and early postoperative blood loss. The patient population was stratified in quintiles of transfusional risk, by means of propensity scoring. As to modifiable risk factors, patients in the highest quintiles of risk were those with BSA ( < 1.73, preoperative haemoglobin < 12 g/dl, intraoperative haemoglobin < 8.0 g/dl and those undergoing cardiopulmonary bypass > 90'). Binary segmentation was performed to avoid any association between red cell transfusion and worse outcomes being causative and dose-dependent. A dose-dependent pattern was disclosed, with patients receiving > 5 units being at highest risk. CONCLUSIONS: High exposure to blood transfusions may be prevented by preoperative patient stratification and by the close tailoring of management strategies on planning and implementing surgical timing, as well as by cardiopulmonary bypass technique.

A randomized-controlled pilot study comparing ICD implantation with and without intraoperative defibrillation testing in patients with heart failure and severe left ventricular dysfunction: a substudy of the RAFT trial.

INTRODUCTION: The need to perform defibrillation testing (DT) at the time of implantable cardioverter defibrillator (ICD) insertion is controversial. In the absence of randomized trials, some regions now perform more than half of ICD implants without DT. METHODS: During the last year of enrolment in the Resynchronization for Ambulatory Heart Failure Trial, a substudy randomized patients to ICD implantation with versus without DT. RESULTS: Among 252 patients screened, 145 were enrolled; 75 randomized to DT and 70 to no DT. Patients were similar in terms of age (65.9 ± 9.3 years vs 67.9 ± 8.9 years); LVEF (24.7 ± 4.6% vs 23.6 ± 4.6%), QRS width (154.8 ± 23.5 vs 155.8 ± 23.6 ms), and history of atrial fibrillation (5% vs 6%). All 68 patients in the DT arm tested according to the protocol achieved a successful DT (≤25 J); 96% without requiring any system modification. No patient experienced perioperative stroke, myocardial infarction, heart failure (HF), intubation or unplanned ICU stay. The length of hospital stay was not prolonged in the DT group: 20.2 ± 26.3 hours versus 21.3 ± 23.0 hours, P = 0.79. One patient in the DT arm had a failed appropriate shock and no patient suffered an arrhythmic death. The composite of HF hospitalization or all-cause mortality occurred in 10% of patients in the no-DT arm and 19% of patients in the DT arm (HR = 0.53, 95% CI: 0.21-1.31, P = 0.14). CONCLUSIONS: In this randomized trial, perioperative complications, failed appropriate shocks, and arrhythmic death were all uncommon regardless of DT. There was a nonsignificant increase in the risk of death or HF hospitalization with DT.

Integration of MR images with electroanatomical maps: feasibility and utility in guiding left ventricular substrate mapping.

PURPOSE: The purpose of the study is to evaluate the feasibility and utility of magnetic resonance (MR) image and electroanatomic (EA) maps integration in guiding detailed left ventricle (LV) anatomical and substrate mapping, identifying the most accurate registration strategy. METHODS: Twenty-five patients with dilated ischemic or non-ischemic cardiomyopathy were enrolled. We first verified the feasibility and accuracy of EA mapping and MR image integration using four different strategies (15 patients). Different EA maps were performed according to the strategy in exam: aortic map, collected from the descending portion of the arch to the ascending one; partial or complete LV map, reconstructed with a minimum of 40 widely distributed points or 200 points, respectively. We then evaluated the utility in LV substrate mapping of the most accurate integration method identified (ten patients). RESULTS: Strategy III, based on aortic map and a partial LV map, allowed us to obtain an accurate integration with MR images of aorta and LV with a lower number of EA LV points; we therefore used this strategy during phase II of the study. Both mean LV end diastolic volume and long- and short-axis LV end diastolic diameters obtained by MR were not significantly different compared with Carto measurements. Eighty-eight percent of the segments with transmural/subendocardial scar detected by delayed enhanced MR were localized on bipolar voltage maps projected on MR-integrated images. CONCLUSION: This study shows that integration strategy III represents the optimal registration method. Its clinical utility consists on guiding the catheter roving inside the chamber, mapping all areas of the LV and optimizing scar reconstruction.

Proarrhythmic risk of embryonic stem cell-derived cardiomyocyte transplantation in infarcted myocardium.

BACKGROUND: Cellular replacement strategies using embryonic stem cells (ESCs) and their cardiac derivatives are emerging as novel experimental therapeutic paradigms for the treatment of post-myocardial infarction (MI) left ventricular (LV) dysfunction; however, their potential proarrhythmic risk remains unclear. OBJECTIVE: The purpose of this study was to investigate the functional effect and proarrhythmic risk of ESC transplantation in a mouse model of MI. METHODS: We compared the functional effects and proarrhythmic risk of direct intramyocardial transplantation of 3 × 10(5) undifferentiated mouse ESCs (MI+ESC group, n = 33) and mouse ESC-derived cardiomyocytes (MI+ESC-CM group, n = 40) versus culture medium (MI group, n = 33) at the infarct border zone in a mouse model of acute MI. LV performance was assessed with serial cardiac magnetic resonance imaging (MRI) at 1 and 3 week(s) post-MI, and invasive LV pressure measurement was assessed (dP/dt) at 4 weeks before sacrifice for histological examination. Furthermore, electrophysiological study was also performed in another set of animals in each group (n = 24) to assess for proarrhythmias after transplantation. RESULTS: In vitro cellular electrophysiological study demonstrated that ESC-CMs exhibit arrhythmogenesis including automaticity, lengthened action potential duration, and depolarized resting membrane potential. At 4 weeks, the MI+ESC-CM group (21/40, 53%) had a higher mortality rate compared with those in the MI group (10/33, 30%, P = .08) and in the MI+ESC group (7/33, 21%, P = .012). Electrophysiological study showed a significantly higher incidence of inducible ventricular tachyarrhythmias in the MI+ESC-CM group (13/24, 54%) compared with in the MI group (6/24, 21%, P = .039) and in the MI+ESC group (5/24, 21%, P = .017). Cardiac MRI showed similar improvement in LV ejection fraction in the MI+ESC and MI+ESC-CM groups compared with in the MI group at 1 week (27.5% ± 3.8%; 30.3% ± 5.2% vs. 12.4% ± 1.4%; P < .05) and 3 weeks (29.8% ± 3.9%; 27.0% ± 4.8% vs. 10.6% ± 2.8%; P < .05) post-MI, respectively. Furthermore, invasive hemodynamic assessment at 4 weeks showed significant similar improvement in LV +dP/dt in the MI+ESC (2,644 ± 391 mmHg/s, P < .05) and MI+ESC-CM groups (2,539 ± 389 mmHg/s; P < .05) compared with in the MI group (2,042 ± 406 mmHg/s). CONCLUSIONS: Our results demonstrate that transplantation of undifferentiated ESCs and ESC-CMs provides similar improvement in cardiac function post-MI. However, transplantation of ESC-CMs is associated with a significantly higher prevalence of inducible ventricular tachyarrhythmias and early mortality than transplantations with ESCs.

Reversion of left ventricular systolic dysfunction and abnormal stress test: by catheter ablation, in a patient with Wolff-Parkinson-White syndrome from Para-Hisian Kent bundle.

The diagnosis of Wolff-Parkinson-White syndrome is typically reserved for patients who experience ventricular pre-excitation and symptoms that are related to paroxysmal supraventricular tachycardia, such as chest pain, dyspnea, dizziness, palpitations, or syncope. Herein, we report the case of a 38-year-old woman who presented at our outpatient department because of exercise intolerance. Cardiac auscultation revealed a grade 2/6 pansystolic murmur over the left lower sternal border. Twelve-lead electrocardiography showed sinus rhythm at a rate of 76 beats/min, with a significant delta wave. Transthoracic echocardiography revealed abnormal left ventricular systolic function. The results of a thallium stress test were also abnormal. Coronary artery disease was suspected; however, coronary angiography yielded normal results. Electrophysiologic study revealed a para-Hisian Kent bundle and a dual atrioventricular nodal pathway. After radiofrequency catheter ablation was performed, the patient's left ventricular function improved and her symptoms disappeared. In Wolff-Parkinson-White syndrome, left ventricular systolic dyssynchrony can yield abnormal findings on echocardiography and thallium scanning--even in persons who have no cardiovascular risk factors. Physicians who are armed with this knowledge can avoid performing coronary angiography unnecessarily. Catheter ablation can reverse the dyssynchrony of the ventricle and improve the patient's symptoms.

Neurogenic stunned myocardium after acute hydrocephalus.

Neurogenic stunned myocardium (NSM) is a syndrome of cardiac stunning after a neurological insult. It is commonly observed after aneurysmal subarachnoid hemorrhage but is increasingly being reported after other neurological events. The underlying mechanism of NSM is believed to be a hypothalamic-mediated sympathetic surge causing weakened cardiac contractility and even direct cardiac myocyte damage. The authors report 2 cases of NSM in pediatric patients after acute hydrocephalus. Both patients experienced severe cardiac dysfunction in the acute phase but ultimately had a good neurological outcome and a full cardiac recovery. The identification, treatment, and outcome in 2 rare pediatric cases of NSM are discussed, and the history of the brain-cardiac connection is reviewed.

Dominant frequency differences in atrial fibrillation patients with and without left ventricular systolic dysfunction.

AIMS: The aim of this study was to determine the mechanisms of atrial fibrillation (AF) in patients with left ventricular systolic dysfunction (LVSD). METHODS AND RESULTS: Dominant frequency (DF) spatiotemporal stability was studied in 15 patients with persistent AF (PEAF) and LVSD (Group I), 15 with PEAF without LVSD (Group II), and 10 with paroxysmal AF (PAAF) without LVSD (Group III). Dominant frequencies were analysed at 536 sites at baseline (DF1) and 26 +/- 12 min later (DF2). A DF1-DF2 difference of

Cardiomyopathy induced by adenosine-insensitive atrial tachycardia.

Tachycardia-induced cardiomyopathy may be provoked by several arrhythmias; it may reverse following stable restoration of sinus rhythm. We report the case of a 33-year-old man who was diagnosed to have a dilated cardiomyopathy. Over a few months, the cardiomyopathy reversed. Subsequently, atrial tachycardia, associated with a recurrent impairment of left ventricular function, occurred. Adenosine infusion during atrial tachycardia caused transient atrioventricular block without the interruption of arrhythmia, which is consistent with a micro-reentrant mechanism. Electroanatomic mapping during tachycardia showed a focus arising from the left superior pulmonary vein ostium. After successful catheter ablation of the focus, left ventricular function fully recovered.

Catheter ablation of premature ventricular contraction-induced cardiomyopathy.

BACKGROUND: A 44-year-old female presented with a long history of chest pain, palpitations and increasing dyspnea. Electrocardiography and 24 h Holter monitoring revealed multiple premature ventricular complexes (PVCs), and echocardiography demonstrated significant left ventricular dilatation and systolic impairment. After further investigation it was concluded that this cardiomyopathy was secondary to the observed multiple PVCs and that these represented a potential target for treatment. INVESTIGATIONS: Electrocardiography, echocardiography, cardiac MRI, 24 h Holter monitoring, coronary angiography, tilt testing and invasive electrophysiological testing using a multielectrode array catheter. DIAGNOSIS: PVC-induced dilated cardiomyopathy. MANAGEMENT: Electrophysiological mapping and cryoablation of the focus of the ventricular ectopy.

Cell transplantation for treatment of left-ventricular dysfunction due to ischemic heart failure: from bench to bedside.

Cell transplantation is an innovative technology that involves the implantation of a variety of myogenic and angiogenic cell types. The transplanted cells proliferate and augment left ventricular performance and therein ameliorate the heart failure symptoms. The concept of cell transplantation has followed the footsteps of angiogenesis starting as bench side research. The latter half of the decade saw the transformation of this potential mechanism to a promising therapy for ischemic heart failure. More than 150 patients have been treated with cellular transplantation worldwide. This novel application has the potential to revolutionize alternative therapeutic approaches to management of heart failure.

Safety of intramyocardial injection of autologous bone marrow cells to treat myocardial ischemia in pigs.

OBJECTIVE: The purpose of this study is to determine the potential adverse consequences of intracardiac injections of bone marrow mononuclear cells (BMCs) to facilitate the revascularization of ischemic myocardium. BACKGROUND: Bone marrow mononuclear cells are used to treat heart failure, though there are few studies that evaluated the safety of BMC transplantation for chronic myocardial ischemia. METHODS: The pigs received coronary ameroid constrictors to induce chronic myocardial ischemia and left ventricular dysfunction. At 4 weeks, autologous BMCs were injected intramyocardially by Boston Scientific Stiletto catheter with low-dose (10(7) cells) or high-dose BMC (10(8)). Control animals received saline. Blood samples were collected for hematological and chemical indices, including cardiac enzyme levels at regular time intervals postinfarction. At 7 weeks, animals underwent electrophysiological study to evaluate the arrhythmic potential of transplanted BMC, followed by necropsy and histopathology. RESULTS: No mortalities were associated with intramyocardial delivery of BMC or saline. At Day 0, the total creatine phosphokinase (CPK) was in the normal range in all groups. All groups had significant elevations in CPK after ameroid placement, with no significant differences between groups. At 7 weeks, CPK in all groups had returned to pretreatment levels. Electrophysiological assessment revealed that one control animal had an inducible arrhythmia. No arrhythmias were induced in low- or high-dose BMC-treated pigs. There were no histopathological changes associated with BMC injection. CONCLUSION: This study showed, in a clinically relevant large-animal model, that catheter-based intramyocardial injection of autologous BMC into ischemic myocardium is safe.

Refractory ventricular tachycardia secondary to cardiac sarcoid: electrophysiologic characteristics, mapping, and ablation.

BACKGROUND: Cardiac sarcoidosis is a recognized cause of ventricular tachycardia (VT) and sudden death that has not been well studied. OBJECTIVES: The purpose of this study was to describe the clinical characteristics of a consecutive series of eight patients with recurrent monomorphic VT due to cardiac sarcoidosis and to define the electrophysiologic characteristics of the VT and its electrophysiologic substrate. METHODS/RESULTS: Of 98 patents with nonischemic cardiomyopathy and VT referred for ablation over a 7-year period, sarcoid was the etiology in 8%. Mean age was 42 +/- 8 years, and all but one patient had a reduced left ventricular ejection fraction (mean 34% +/- 15%). VT was the initial manifestation of sarcoid disease in 5 of 8 cases based on retrospective analysis. All patients had not responded to therapy with multiple antiarrhythmic drugs (mean 2.5 +/- 1). Cardiac biopsy initially was negative in 3 of 7 patients, and in 2 patients the diagnosis was not made until posttransplant examination of the heart. Two patients (25%) had a previous presumptive diagnosis of arrhythmogenic right ventricular dysplasia. Electrophysiologic study revealed evidence of scar-related reentry with multiple monomorphic VTs induced (4 +/- 2 VTs per patient) with both right bundle branch block and left bundle branch block QRS configurations. Areas of low-voltage scar were present in the right ventricle in all 8 of 8 patients, in the left ventricle in 5 (63%) of 8 patients, and in the epicardium in 2 patients undergoing epicardial mapping. Ablation abolished one or more VTs in 6 (75%) of 8 patients, but other VTs remained inducible in all but one patient. Postablation, some form of sustained VT recurred in 6 of 8 patients within 6 months. However, at longer follow-up (range 6 months to 7 years), 4 of 8 patients currently are free of VT with antiarrhythmic drugs and immunosuppression. Cardiac transplantation eventually was required in 5 of 8 patients because of either recurrent VT (n = 4) or heart failure (n = 1). CONCLUSION: Sarcoid is an important diagnostic consideration in scar-related VT. Sarcoid can be misdiagnosed as idiopathic or arrhythmogenic right ventricular cardiomyopathy. Arrhythmia control can be difficult, although ablation can be helpful in some patients.

Pediatric cardiac remodeling after cardiac resynchronization therapy.

A 1.8-year-old male required a conventional DDD pacemaker for an atrioventricular block after congenital heart surgery. Five years later, heart failure due to left ventricular (LV) dyssynchrony progressed and we performed cardiac resynchronization therapy (CRT). Long-term echocardiographic follow-up showed that LV shortening fraction had improved within the first year after CRT, and LV end diastolic dimension had decreased after the first year. During LV remodeling (1-24 months after CRT), the QRS duration shortened without a change in the JT and T (peak-end) interval. The New York Heart Association class improved from III to I during the 2.3-year follow-up.

Bioenergetic and functional consequences of stem cell-based VEGF delivery in pressure-overloaded swine hearts.

In an established swine model of severe left ventricular (LV) hypertrophy (LVH), the bioenergetic and functional consequences of transplanting autologous mesenchymal stem cells (MSCs) overexpressing vascular endothelial growth factor (VEGF-MSCs) into the LV were evaluated; transplantation was accomplished by infusion of VEGF-MSCs into the interventricular cardiac vein. Specifically, the hypertrophic response to aortic banding was compared in seven pigs treated with 30 million VEGF-MSCs, eight pigs treated with 30 million MSCs without VEGF modification, and 19 untreated LVH pigs. Eight pigs without banding or cell transplantation (normal) were also studied. Four weeks postbanding, LV wall thickening (MRI), myocardial blood flow (MBF), high-energy phosphate levels ((31)P magnetic resonance spectroscopy), and hemodynamic measurements were obtained under basal conditions and during a catecholamine-induced high cardiac workstate (HCW). Although 9 of 19 untreated banded pigs developed clinical evidence of biventricular failure, no MSCs-treated animal developed heart failure. MSCs engraftment was present in both cell transplant groups, and both baseline and HCW MBF values were significantly increased in hearts receiving VEGF-MSCs compared with other groups (P < 0.05). During HCW, cardiac inotropic reserve (defined as the percent increase of rate pressure product at HCW relative to baseline) was normal in the VEGF-MSCs group and significantly decreased in all other banded groups. Additionally, during HCW, the myocardial energetic state [reflected by the phosphocreatine-to-ATP ratio (PCr/ATP)] of VEGF-MSCs-treated hearts remained stable, whereas in all other groups, PCr/ATP decreased significantly from baseline values (P < 0.05, each group). Myocardial von Willebrand factor and VEGF mRNA expressions and myocardial capillary density were significantly increased in VEGF-MSCs-treated hearts (P < 0.05). Hence, in the pressure-overloaded LV, transplantation of VEGF-MSCs prevents LV decompensation, induces neovascularization, attenuates hypertrophy, and improves MBF, myocardial bioenergetic characteristics, and contractile performance.