Leonard S. Lilly

Assessment of autonomic regulation in chronic congestive heart failure by heart rate spectral analysis.

Neurohumoral modulation of cardiovascular function is an important component of the hemodynamic alterations in patients with chronic congestive heart failure (CHF). Analysis of heart rate (HR) variability is a noninvasive means of investigating the autonomic control of the heart. The variability of HR and respiratory signals, both derived from ambulatory electrocardiographic recordings, were analyzed with power spectral analysis to evaluate autonomic control in 25 patients with chronic stable CHF (class III or IV) and 21 normal control subjects. In the patients with CHF, HR spectral power was markedly reduced (p less than 0.0001) at all frequencies examined (0.01 to 1.0 Hz, period 1 to 100 seconds) and virtually absent at frequencies greater than 0.04 Hz. Heart rate fluctuations at very low frequencies (0.01 to 0.04 Hz) less effectively differentiated CHF patients from control subjects, due to discrete (about 65 seconds, 0.015 Hz) oscillation in HR, which was associated with a similar pattern in respiratory activity in many of the patients with CHF. These findings demonstrate a marked derangement of HR modulation in patients with severe CHF. The frequency characteristics of HR fluctuations in these patients are consistent with abnormal baroreflex responsiveness to physiologic stimuli, and suggest that there is diminished vagal, but relatively preserved sympathetic, modulation of HR.

Prostaglandins in severe congestive heart failure. Relation to activation of the renin--angiotensin system and hyponatremia.

To determine whether prostaglandins are involved in circulatory homeostasis in congestive heart failure, we measured plasma levels of the metabolites of vasodilator prostaglandins I2 and E2 in 15 patients with severe chronic heart failure. Mean circulating levels of both metabolites were 3 to 10 times higher than those in normal subjects. Plasma levels of both metabolites correlated directly with plasma renin activity and plasma angiotensin II concentrations (r = 0.64 and 0.84, respectively). Individual serum sodium concentrations were inversely correlated with levels of prostaglandin E2 metabolites (r = -0.92, P less than 0.001) and plasma renin activity (r = -0.69, P less than 0.02). Of 23 patients with severe heart failure challenged with indomethacin (an inhibitor of prostaglandin synthesis), the 9 with hyponatremia had significant decreases in the cardiac index (1.99 +/- 0.12 to 1.72 +/- 0.13 liters per minute per square meter of body-surface area, P less than 0.001) and significant increases in the pulmonary capillary wedge pressure (17.4 +/- 2.0 to 24.0 +/- 1.9 mm Hg, P less than 0.001) and systemic vascular resistance (1882 +/- 239 to 2488 +/- 315 dyn x sec x cm-5, P less than 0.001), whereas the 14 patients with a normal serum sodium concentration had no significant hemodynamic changes. We conclude that both vasoconstrictor (renin-angiotensin) and vasodilator (prostaglandin) mechanisms are operative in patients with heart failure complicated by hyponatremia and that these mechanisms interact to modulate circulatory homeostasis.

Power spectrum analysis of heart rate variability in human cardiac transplant recipients.

Beat-to-beat heart rate variability was studied by power spectral analysis in 17 orthotopic cardiac transplant patients. Heart rate power spectra were calculated from eighty-four 256-second recordings and compared with those taken from six normal subjects. The power spectra from the control subjects resolved into discrete peaks at 0.04-0.12 Hz and 0.2-0.3 Hz, whereas those of heart transplant recipients resembled broad-band noise without peaks. Log total power in the 0.02-1.0 Hz range was greater in the control subjects (0.982 +/- 0.084 [0.206], mean +/- SEM [SD]) than in the transplanted subjects (-0.766 +/- 0.059 [0.541]), (p less than 0.0001). Fifty-five electrocardiographic recordings from transplant patients were done within 48 hours of an endomyocardial biopsy. When the power spectra of those patients whose endomyocardial biopsies showed evidence of myocardial rejection were compared with those from patients who were found to be free of rejection, a significant difference was found in log total power (-0.602 +/- 0.090 [0.525] vs. -0.909 +/- 0.136 [0.577], p less than 0.02). We conclude that denervation of the heart significantly reduces heart rate variability and abolishes the discrete spectral peaks seen in untransplanted control subjects and that the development of allograft rejection may significantly increase heart rate variability.

Renin expression by vascular endothelial cells in culture.

Cultured bovine aortic endothelial cells were examined for renin activity by biochemical, immunological, and immunohistochemical techniques. When cell sonicates were incubated with renin substrate, linear generation of angiotensin I was observed (1.12 +/- 0.2 ng angiotensin I/10(6) cells per hr). The effect of pH on this activity was similar to that of bovine renal renin, and renin antibodies inhibited a large portion of the enzymatic activity. Furthermore, immunofluorescence microscopy with antirenin antisera confirmed the presence of renin within these cells. Biosynthetic radiolabeling, followed by immunoprecipitation, demonstrated de novo synthesis of a renin precursor in the endothelial cells, which was processed to a more mature protein. Thus, bovine aortic endothelial cells in culture contain and biosynthesize renin, a key component of the renin-angiotensin system. The expression of renin activity by endothelium may contribute to the local regulation of vascular tone.

Treatment of Acute and Recurrent Idiopathic Pericarditis

Case Presentation: A 56-year-old previously healthy man presented with 2 days of pleuritic left anterior chest pain, lessened by sitting forward. His examination was pertinent for low-grade fever (37.6°C), blood pressure 122/76 mm Hg without paradox, no jugular venous distension, clear lungs, and a 3-component pericardial friction rub. The ECG showed diffuse concave-upward ST-segment elevation and PR-segment depression in the inferior leads. The serum C-reactive protein level was 64 mg/L, and the cardiac troponin T was not elevated. Echocardiography showed normal left ventricular contractile function without wall motion abnormalities and no pericardial effusion. He was diagnosed with acute pericarditis, and the symptoms responded promptly to oral ibuprofen, continued for 2 weeks. Six weeks later, he redeveloped pleuritic chest pain and clinical and ECG findings identical to the initial presentation. His primary care physician asks for advice about appropriate therapy. Pericarditis accounts for 5% of emergency department visits for chest pain in the absence of myocardial infarction.1 In ≈80% of cases in developed countries, the cause of pericarditis is either postviral or “idiopathic,” in that it cannot be attributed to a specific condition.2,3 Because these 2 etiologies are clinically equivalent, the term idiopathic pericarditis will refer to both in this Clinician Update. Even when managed effectively, many patients with acute pericarditis present with 1 or more repeated episodes, termed recurrent pericarditis .4 Treatment of idiopathic pericarditis has long been empirical, because until recently, there have been few therapeutic trials addressing this condition. The European Society of Cardiology published the only treatment guideline for pericarditis almost a decade ago, and many of the recommendations were based on opinion because of the lack of available study evidence.4 Most patients with idiopathic pericarditis experience self-limited symptoms that improve spontaneously within days to weeks. More rapid relief can be …

Initial Presentation of an Accessory Left Ventricle in a Patient With Syncope

A 39-year-old woman was referred for a transthoracic echocardiogram after presenting to her primary care provider following an episode of unexplained loss of consciousness. Her past medical history was notable for fibromyalgia and migraine headaches. She had a normal cardiac and neurological physical examination with no extra heart sounds or murmurs. Her transthoracic echocardiogram (Movie I of the online-only Data Supplement) revealed a large outpouching of the lateral wall of the left ventricle (LV) that contracted in synchrony with the ventricle (Figure 1A and 1B). The initial differential for this finding included an LV diverticulum or an accessory ventricle. An LV pseudoaneurysm was considered unlikely because of the synchronous contraction of the outpouching with the rest of the ventricle. Figure 1. Transthoracic echocardiogram demonstrating the apical 4-chamber view of the LV. The outpouching (arrow) originating from the lateral aspect of the midventricular wall is shown in both diastole (A) and systole (B). The outpouching contracted synchronously with the LV. To further evaluate this …

Response to Letter Regarding Article “Treatment of Acute and Recurrent Pericarditis”

I appreciate the comments of Drs Chhabra and Spodick regarding the April 23, 2013 clinician update Treatment of Acute and Recurrent Idiopathic Pericarditis .1 The focus of that article is the contemporary therapy of postviral/idiopathic pericarditis, the foundation of which is nonsteroidal anti-inflammatory therapy and colchicine while reserving …

Etiologies of Pericardial Diseases

There is a wide spectrum of conditions that affect the pericardium, including congenital defects and cysts, infectious, immune-mediated, metabolic, traumatic, neoplastic and drug-related causes [1] (Table 2.1). Most of these disorders result from an extrapericardial process (e.g., viral infections, uremia, chest radiation therapy), whereas a minority are isolated to the pericardium itself (e.g., cysts). Pathologically, the two most common disease processes are pericarditis (i.e., inflammation) and pericardial effusion. A less frequent development is pericardial constriction, a consequence of inflammatory insults that results in thickening, fibrosis and calcification [2]. Clinically, the presentation of pericardial disease is primarily determined by the degree and chronicity of the inflammatory process, the rate and amount of effusion accumulation, and the degree of any pericardial thickening and fibrosis. The etiology of most cases of acute pericarditis is deemed “idiopathic” as no specific diagnosis is actively sought [3, 4]. The majority of such episodes are believed to be of viral origin.