Ramesh Hariharan

Fundamental Limitations of [18F]2-Deoxy-2-Fluoro-d-Glucose for Assessing Myocardial Glucose Uptake

BACKGROUND The glucose tracer analog [18F]2-deoxy-2-fluoro-D-glucose (FDG) is widely used for assessing regional myocardial glucose metabolism in vivo. The reproducibility of this method has recently been questioned because of a discordant affinity of hexokinase for its substrates glucose and 2-deoxyglucose. We therefore compared rates of glucose utilization simultaneously with tissue time-activity curves of FDG uptake before and after changes in the physiological environment of the heart. METHODS AND RESULTS Isolated working rat hearts were perfused for 60 minutes with recirculating Krebs buffer containing glucose (10 mmol/L), FDG (1 microCi/mL), [2-3H]glucose (0.05 microCi/mL), and [U-14C]2-deoxyglucose (2-DG; 0.025 microCi/mL). Myocardial glucose uptake was measured by tracer ([2-3H]glucose) and tracer analog methods (FDG and 2-DG) before and after the addition of either insulin (1 mU/mL), epinephrine (1 mumol/L), lactate (40 mmol/L), or D,L-beta-hydroxybutyrate (40 mmol/L) at 30 minutes of perfusion and after acute changes in cardiac workload. Under steady-state conditions, myocardial rates of glucose utilization as measured by tritiated water (3H2O) production from metabolism of [2-3H]glucose, FDG uptake, and 2-DG retention were linearly related. The addition of competing substrates decreased glucose utilization immediately. The addition of insulin increased the rate of glucose utilization as measured by the glucose tracer but not as measured by the tracer analogs. The ratio of 3H2O release/myocardial FDG uptake increased by 111% after the addition of insulin, by 428% after the addition of lactate, and by 232% after the addition of beta-hydroxybutyrate. Epinephrine increased rates of glucose utilization and contractile performance, whereas there was no increase in glucose uptake with a comparable increase in workload alone. There was no change in the relation between the glucose tracer and the tracer analog either with epinephrine or with acute changes in workload. CONCLUSIONS The uptake and retention of FDG in heart muscle is linearly related to glucose utilization only under steady-state conditions. Addition of insulin or of competing substrates changes the relation between uptake of the glucose tracer and FDG. These observations preclude the determination of absolute rates of myocardial glucose uptake by the tracer analog method under non-steady-state conditions.

Lower Loop Reentry as a Mechanism of Clockwise Right Atrial Flutter

Background—Right atrial reentrant tachycardia resulting from lower loop reentry (LLR) around the inferior vena cava (IVC) has been described recently. However, all reported cases of LLR in the literature have negative flutter waves on the inferior surface ECG leads similar to that of counterclockwise typical atrial flutter around the tricuspid annulus (TA). Right atrial flutter with positive flutter waves in the inferior ECG leads has been assumed to rotate as a single reentrant activation wave front around the TA, and the role of LLR in those patients is not known. Methods and Results—Twelve consecutive patients with flutter wave morphology on surface ECG consistent with clockwise atrial flutter were studied. The endocardial activation pattern recorded from conventional multipolar electrode catheters was characteristic of clockwise atrial flutter around the TA. Entrainment pacing in all 12 patients and 3D activation sequence mapping in 7 patients, however, revealed clockwise LLR involving the lower right atrium around the IVC in 7 patients, figure-of-8 double-loop reentry around both the IVC and TA in 4, and single reentrant loop around the TA in 1. Linear radiofrequency ablation in the isthmus between the TA and IVC (TI isthmus) terminated the tachycardia in all patients. Conclusions—Surface ECG flutter wave morphology and limited recording intracardiac sites proved insufficient to delineate the precise mechanism of the TI isthmus–dependent clockwise right atrial flutters. Most right atrial flutters with positive flutter wave on surface ECG may be supported by a reentrant circuit around the IVC or a figure-of-8 double-loop reentry involving both the IVC and TA.

No electromagnetic interference occurred: In a patient with a heartmate ii left ventricular assist system and a subcutaneous implantable cardioverter-defibrillator

The use of subcutaneous implantable cardioverter-defibrillators is a novel option for preventing arrhythmia-mediated cardiac death in patients who are at risk of endovascular-device infection or in whom venous access is difficult. However, the potential for electromagnetic interference between subcutaneous defibrillators and left ventricular assist devices is largely unknown. We report the case of a 24-year-old man in whom we observed no electromagnetic interference between a subcutaneous implanted cardioverter-defibrillator and a HeartMate II Left Ventricular Assist System, at 3 different pump speeds. To our knowledge, this is the first report of such findings in this circumstance.

Minimal use of fluoroscopy to reduce fetal radiation exposure during radiofrequency catheter ablation of maternal supraventricular tachycardia.

Electrophysiologic procedures in the young engender concern about the potential long-term effects of radiation exposure. This concern is manifold if such procedures are contemplated during pregnancy. Catheter ablations in pregnancy are indicated only in the presence of an unstable tachycardia that cannot be controlled by antiarrhythmic agents. This report describes the case of an 18-year-old pregnant woman and our stratagem to minimize irradiation of the mother and the fetus.

Pleural and Pericardial Effusions in a 50-Year-Old Woman

A previously healthy 50-year-old Chinese woman presented with a low-grade fever, a generalized headache, and chest pain of 2 to 3 weeks’ duration. She described intermittent sharp chest pain over the precordium that intensified when she lay down and shortness of breath after minimal exertion. Despite having lost her appetite, she had gained ≈10 pounds during the past month and had noticed ankle swelling. She denied having had arthralgia or skin rash and had not experienced any nocturnal dyspnea, wheezing, cough, expectoration, or hemoptysis. She had visited her relatives in the Middle East 6 months earlier, but her past medical history was uneventful. She had taken acetaminophen (Tylenol) tablets and a Chinese herbal preparation, but her symptoms continued. On physical examination, she appeared weak and ill. Her temperature was 36.7°C (98.0°F), and her pulse was 110 beats per minute, regular, and had normal volume and character. Her blood pressure was 115/70 mm Hg, which decreased to 90/70 mm Hg on inspiration; her respiratory rate was 22 breaths per minute. Carotid pulsations were normal. Jugular veins were distended to the angle of the mandible when the patient sat upright, but no further venous engorgement was noted on inspiration. There was mild mucosal pallor, but the oropharynx was otherwise normal. The first and second heart sounds were normal, and there were no clicks or gallops. A superficial scratchy systolic sound was heard intermittently over the left lower sternal region. Dullness to percussion, scattered inspiratory crackles, and diminished air entry were evident over both lung bases. Abdominal examination demonstrated a soft, tender liver palpable 2 cm below the right costal margin. Her pelvis and rectum showed no abnormality. A stool guaiac test was negative. Neurological examination was normal. There was moderate pitting edema below the level of the knees. Results of the initial …

1 A Multi-Sensor Algorithm Predicts Heart Failure Events in Patients with Implanted Devices: Results from the MultiSENSE Study

Purpose: Toevaluate toperformanceof analgorithmdevelopedusing diagnostic sensor data from implanted cardiac resynchronization therapy defibrillators (CRT-D) to detect impending heart failure decompensation events. Background: Heart Failure (HF), a growing health-care challenge globally, involves costly hospitalizations with adverse impact on patient outcomes. Reliable monitoring for early signs of worsening HF is needed to enable proactive interventions for prevention of acute decompensations. We hypothesize that an algorithm combining information from a diverse set of implanted device based sensors judiciously chosen to target different aspects of HF pathophysiology can effectively detect worsening HF. Methods: MultiSENSE enrolled patients with HF and reduced EF (HFrEF) implanted with CRT-D, converted into an investigational device to enable chronic ambulatory data collection. HF events (HFEs) were defined as HF admissions or unscheduled visits with augmented intravenous HF treatment, and were independently adjudicated. Patients were assigned to Development or Test set cohorts in chronological order of enrollment. The development set was used to construct a composite index and alert algorithm (HeartLogic) combining Heart Sounds, Respiration, Thoracic Impedance, Heart Rate and Activity; whereas the test set was sequestered for its subsequent independent validation. Sensitivity was defined as the proportion of usable HFEs detected by HeartLogic alerts. Unexplained alert rate (UAR)was defined as the ratio of alerts not explained by HF to the total usable follow-up duration. The two co-primary endpoints: 1. Sensitivity performance goal (PG) of> 40%; 2. UAR PG of< 2 alerts per patient year were testedwith a 2-sided 95% confidence interval (CI). Results: Overall, 900 (Development 1⁄4 500, Test 1⁄4 400) patients had sensor data collection enabled and followed for up to a year. Primary endpoints were evaluated using the 320 patient years of follow-up data and 50 adjudicated usable HFEs in the Test Set cohort (72% male; age 66.8 10.3 years; NYHA Class at enrollment I/II/III/IV/unknown: 5%/69%/25%/1%/1%; LVEF 30.0 11.4%). With an observed sensitivity of 70% (Lower 2-sided 95% CI: 55.4%) and UAR of 1.47 (Upper 2-sided 95% CI: 1.65), both endpoints were significantly exceeded. Conclusion: The HeartLogic multi-sensor HF diagnostic algorithm significantly exceeded its pre-specified endpoints demonstrating compelling performance for worsening HF detection.