Heart rate-induced modifications of concentric left ventricular hypertrophy: exploration of a novel therapeutic concept.

Lowering the heart rate is considered to be beneficial in heart failure (HF) with reduced ejection fraction (HFrEF). In a dilated left ventricle (LV), pharmacological heart rate lowering is associated with a reduction in LV chamber size. In patients with HFrEF, this structural change is associated with better survival. HF with preserved ejection fraction (HFpEF) is increasingly prevalent but, so far, without any evidence-based treatment. HFpEF is typically associated with LV concentric remodeling and hypertrophy. The effects of heart rate on this structural phenotype are not known. Analogous with the benefits of a low heart rate on a dilated heart, we hypothesized that increased heart rates could lead to potentially beneficial remodeling of a concentrically hypertrophied LV. This was explored in an established porcine model of concentric LV hypertrophy and fibrosis. Our results suggest that a moderate increase in heart rate can be used to reduce wall thickness, normalize LV chamber volumes, decrease myocardial fibrosis, and improve LV compliance. Our results also indicate that the effects of heart rate can be titrated, are reversible, and do not induce HF. These findings may provide the rationale for a novel therapeutic approach for HFpEF and its antecedent disease substrate.

A pacemaker powered by an implantable biofuel cell operating under conditions mimicking the human blood circulatory system--battery not included.

Biocatalytic electrodes made of buckypaper were modified with PQQ-dependent glucose dehydrogenase on the anode and with laccase on the cathode and were assembled in a flow biofuel cell filled with serum solution mimicking the human blood circulatory system. The biofuel cell generated an open circuitry voltage, Voc, of ca. 470 mV and a short circuitry current, Isc, of ca. 5 mA (a current density of 0.83 mA cm(-2)). The power generated by the implantable biofuel cell was used to activate a pacemaker connected to the cell via a charge pump and a DC-DC converter interface circuit to adjust the voltage produced by the biofuel cell to the value required by the pacemaker. The voltage-current dependencies were analyzed for the biofuel cell connected to an Ohmic load and to the electronic loads composed of the interface circuit, or the power converter, and the pacemaker to study their operation. The correct pacemaker operation was confirmed using a medical device - an implantable loop recorder. Sustainable operation of the pacemaker was achieved with the system closely mimicking human physiological conditions using a single biofuel cell. This first demonstration of the pacemaker activated by the physiologically produced electrical energy shows promise for future electronic implantable medical devices powered by electricity harvested from the human body.

Lyme Carditis Complicated by Polymorphic Ventricular Tachycardia and Cardiac Arrest: A Case Report.

Lyme disease is commonly encountered in endemic areas of the United States harboring the causal organism Borrelia burgdorferi. Lyme carditis can manifest in early disseminated infections, usually as atrioventricular nodal blockade. Timely antibiotic therapy typically suppresses myocardial inflammation and reverses cardiac conduction disturbances. We present a case of a previously healthy male who presented to the emergency department with non-prodromal syncope, multifocal annular rashes, and antecedent inflammatory knee pain and effusion, found to have positive 2-tier Lyme testing and pause-dependent polymorphic ventricular tachycardia leading to cardiac arrest. Lyme carditis occurs in early disseminated infections but rarely leads to cardiac arrest. Acute management is entrained in well-established guidelines for therapy, and together with risk stratification scoring can be considered by emergency care physicians in the workup of undifferentiated syncope with concern for Lyme disease with cardiac involvement.

Heart Rate-Induced Myocardial Ca2+ Retention and Left Ventricular Volume Loss in Patients With Heart Failure With Preserved Ejection Fraction.

Background Increases in heart rate are thought to result in incomplete left ventricular (LV) relaxation and elevated filling pressures in patients with heart failure with preserved ejection fraction (HFpEF). Experimental studies in isolated human myocardium have suggested that incomplete relaxation is a result of cellular Ca2+ overload caused by increased myocardial Na+ levels. We tested these heart rate paradigms in patients with HFpEF and referent controls without hypertension. Methods and Results In 22 fully sedated and instrumented patients (12 controls and 10 patients with HFpEF) in sinus rhythm with a preserved ejection fraction (≥50%) we assessed left-sided filling pressures and volumes in sinus rhythm and with atrial pacing (95 beats per minute and 125 beats per minute) before atrial fibrillation ablation. Coronary sinus blood samples and flow measurements were also obtained. Seven women and 15 men were studied (aged 59±10 years, ejection fraction 61%±4%). Patients with HFpEF had a history of hypertension, dyspnea on exertion, concentric LV remodeling and a dilated left atrium, whereas controls did not. Pacing at 125 beats per minute lowered the mean LV end-diastolic pressure in both groups (controls -4.3±4.1 mm Hg versus patients with HFpEF -8.5±6.0 mm Hg, P=0.08). Pacing also reduced LV end-diastolic volumes. The volume loss was about twice as much in the HFpEF group (controls -15%±14% versus patients with HFpEF -32%±11%, P=0.009). Coronary venous [Ca2+] increased after pacing at 125 beats per minute in patients with HFpEF but not in controls. [Na+] did not change. Conclusions Higher resting heart rates are associated with lower filling pressures in patients with and without HFpEF. Incomplete relaxation and LV filling at high heart rates lead to a reduction in LV volumes that is more pronounced in patients with HFpEF and may be associated with myocardial Ca2+ retention.

Multidetector computed tomography guidance in complex cardiac ablations.

Radiofrequency ablation of complex cardiac arrhythmias has undergone significant evolution in the past decade, with the development of technology enabling better anatomic and electrophysiologic mapping of abnormal cardiac tissue. In this paper, we will discuss the role of pre-procedural and post-procedural multidetector computed tomography, with specific focus on the anatomic assessment of pulmonary vein and left atrial anatomy in the ablation of atrial fibrillation. We will also consider how the integration of both multidetector computed tomography and electroanatomic computer-based imaging may contribute more broadly to the management of a variety of complex ablation procedures.

His-bundle pacing versus biventricular pacing in cardiac resynchronization therapy patients: A crossover design comparison.

BACKGROUND: Cardiac resynchronization therapy (CRT) typically is attempted with biventricular pacing (BiVP). One-third of patients are nonresponders. His-bundle pacing (HBP) has been evaluated as an alternative means of effecting CRT because it generates truly physiologic ventricular activation, as evidenced in part by the morphologic identity between normally conducted and paced QRS complexes. OBJECTIVE: The purpose of this study was to assess the feasibility of, and clinical response to, permanent HBP as an alternative to BiVP in CRT-indicated patients. METHODS: Patients were implanted with a right atrial pacing lead, defibrillation lead, left ventricular (LV) lead via the coronary sinus, and HBP lead. His and LV leads were plugged into the LV port via a Y-adapter. After successful implant, patients were randomized in single patient-blinded fashion to either HBP or BiVP. After 6 months, patients were crossed over to the other pacing modality and followed for another 6 months. Quality-of-life assessments, echocardiographic measurements, New York Heart Association classification, and 6-minute hall walk test were obtained at baseline and at each 6-month follow-up. RESULTS: Twenty-nine patients were enrolled; 21 (72%) demonstrated electrical resynchronization (QRS narrowing) at implant. Twelve patients completed the crossover analysis at 1 year. Clinical outcomes (quality of life, New York Heart Association functional class, 6-minute hall walk test, LV ejection fraction) were significantly improved for both pacing modes compared with baseline measures. CONCLUSION: In this crossover comparison between HBP and BiVP, HBP was found to effect an equivalent CRT response. QRS narrowing was observed in 21 of 29 patients, suggesting this approach may be feasible in more patients with left bundle branch block than previously assumed.

Electrical resynchronization induced by direct His-bundle pacing.

BACKGROUND: Biventricular pacing (BiV) to effect cardiac resynchronization therapy can be technically difficult and fails to elicit a clinical response in 30% to 40% of patients. Direct His-bundle pacing (DHBP) theoretically could obviate some of these problems. Although DHBP is capable of narrowing the QRS in some patients, the consistency with which this can be achieved has not been characterized. OBJECTIVE: The purpose of this study was to restore His-Purkinje functionality in consecutive patients undergoing de novo clinically mandated cardiac resynchronization therapy. METHODS: DHBP was temporarily implemented at the time of implantation of a permanent BiV system in patients referred for cardiac resynchronization therapy. Native conduction, DHBP, and BiV QRS duration were compared. All patients presenting for BiV cardiac resynchronization therapy were eligible for the study. Ten patients were studied. RESULTS: DHBP was successfully implemented in all 10 patients. In 7 of 10 patients, DHBP narrowed the QRS significantly compared with native conduction and BiV (mean QRS duration: native 171 +/- 13 ms, DHBP 148 +/- 11 ms, BiV 158 +/- 21, P <.0001). QRS narrowing with DHBP was specifically attributable to capture of latent His-Purkinje tissue. DHBP lead implantation time (16 minutes) was shorter than standard left ventricular lead implantation time (42 minutes). CONCLUSION: DHBP was readily implemented in patients with standard indications for BiV cardiac resynchronization therapy. In most patients studied, DHBP resulted in a significantly narrower QRS compared with native conduction. DHBP may offer a physiologic alternative to BiV for cardiac resynchronization therapy.

Treatment of Arrhythmias in Patients with Congestive Heart Failure.

Both ventricular and atrial arrhythmias are commonly encountered in patients with ventricular dysfunction. In fact, roughly half of the deaths occurring in patients with ventricular dysfunction are caused by ventricular arrhythmias. Atrial arrhythmias in this patient population compromise left ventricular filling and if uncontrolled can exacerbate (and in some cases cause) the underlying myopathic process. Consequently, the diagnosis and treatment of these complex, and often life-threatening, arrhythmias is a critical component in the management of congestive heart failure (CHF). As the complexity of pharmacologic and nonpharmacologic antiarrhythmic therapy evolves, it has become increasingly important to understand the potential benefits and limitations of the various treatment modalities in the setting of patients with CHF. The management of arrhythmias in patients with CHF includes conventional drug therapies, as well as therapies directed specifically at treating the arrhythmias that are encountered. The treatment of atrial arrhythmias may include anticoagulation, drugs for rate control, rhythm control, or radiofrequency ablation. The treatment of ventricular arrhythmias, conversely, uses the implantable cardioverter-defibrillator to prevent sudden death, with adjuvant drug therapy or ablation for refractory ventricular tachycardia. This article provides an overview of the current state-of-the-art arrhythmia management in patients with CHF.

Effects of castration on female rabbit bladder physiology and morphology.

OBJECTIVES: To determine the effect of ovariectomy on bladder blood flow and oxygen tension. Women are subject to bladder dysfunctions that occur less frequently in men. These include interstitial cystitis (syndrome of urgency, frequency, and pain on distension), incontinence, and bladder infections. It is believed that alterations in female sex hormones play a major role in mediating these abnormalities. We believe that alterations in estrogen can have marked effects on the blood flow to the bladder. METHODS: We divided 20 female rabbits into two equal groups: ovariectomized and sham operated. Six weeks later, the bladder of each rabbit was evaluated for bladder capacity, compliance, permeability, blood flow, tissue hypoxia, morphology, and smooth muscle contraction. RESULTS: Ovariectomy resulted in decreased bladder compliance; decreased blood flow to the bladder mucosa and uterus, a smaller decrease in blood flow to the bladder smooth muscle, and mucosal hypoxia; and statistically significant thinning of the bladder mucosa and increased mucosal permeability. CONCLUSIONS: Ovariectomy resulted in decreased blood flow and hypoxia to the bladder mucosa and a mildly decreased blood flow to the smooth muscle. The decreased blood flow and hypoxia may be related to the age-related uropathologic findings in postmenopausal women.