Changes in 24-hour heart rate variability during normal pregnancy.

OBJECTIVE: We studied the effects of normal pregnancy on heart rate variability as a noninvasive index of maternal cardiovascular autonomic modulation. STUDY DESIGN: Twenty-four-hour Holter recordings were obtained for 8 healthy pregnant volunteers during early pregnancy (

Relationship of the fourth heart sound to atrial systolic transmitral flow deceleration.

The fourth heart sound (S4) is thought to be due to cardiohemic vibrations, powered by deceleration of transmitral blood flow, that occur when atrial systole leads to a disproportionately high rise in ventricular end-diastolic pressure (relative to diastasis), associated with an enhanced atrial systolic blood filling volume or a stiff ventricular wall. To characterize S4 production, we modeled the cardiohemic system as a forced, damped nonlinear harmonic oscillator. The forcing term used a closed-form expression for the Doppler A-wave contour. We simultaneously recorded transthoracic phonocardiograms and Doppler A waves in subjects with and without audible S4 and compared model predictions for S4 amplitude, frequency, and power spectrum with those of the recorded S4. Excellent agreement was observed between the model-predicted amplitude, duration, timing, and power spectrum and those of the phonocardiographic S4. We conclude that, with a normal mitral valve, there should always be an oscillation of the cardiohemic system during A-wave deceleration. However, oscillations may not have high enough amplitude, frequency, or coupling to the chest wall to be clinically audible as an S4.

Unusual accelerated progression of saccular aneurysms in an ectatic right coronary artery.

Localized aneurysmal dilation or ectasia of coronary arteries is a relatively uncommon angiographic finding, of which the pathophysiological mechanism remains speculative. The majority of patients diagnosed with this clinical entity usually present with angina pectoris. Furthermore, it is rare to find isolated ectasia or aneurysm dilation of the coronary arteries in patients with no prior history of coronary artery disease. The natural course is usually slowly progressive. This case demonstrates an unusual accelerated dilation of coronary saccular aneurysms, within a year of diagnosis, in a patient who presented with new onset congestive heart failure. Although the diagnosis was made with coronary angiography, both magnetic resonance imaging and transesophageal echocardiography were of critical diagnostic value to identify the size and extension of the aneurysms as well as the presence of intraluminal thrombi.

Thrombosis of mitral valve bioprostheses in patients requiring circulatory assistance.

Two patients with new mitral valve bioprostheses required implantation of Bio-Medicus centrifugal pumps (Bio-Medicus, Minneapolis, MN) for circulatory support and had evidence of prosthetic valve thrombosis 1 and 4 days later. Both patients died of thromboembolic complications despite surgical removal of the thrombus. Thrombosis is a rare early complication of bioprosthetic valves and in these cases was probably related to low transvalvular flow due to the use of circulatory assist devices. We discuss possible strategies for avoiding and managing this catastrophic complication.

Relationship of the third heart sound to transmitral flow velocity deceleration.

BACKGROUND: The third heart sound (S3) occurs shortly after the early (E-wave) peak of the transmitral diastolic Doppler velocity profile (DVP). It is thought to be due to cardiohemic vibrations powered by rapid deceleration of transmitral blood flow. Although the presence, timing, and clinical correlates of the S3 have been extensively characterized, derivation and validation of a causal, mathematical relation between transmitral flow velocity and the S3 are lacking. METHODS AND RESULTS: To characterize the kinematics and physiological mechanisms of S3 production, we modeled the cardiohemic system as a forced, damped, nonlinear harmonic oscillator. The forcing term used a closed-form mathematical expression for the deceleration portion of the DVP. We tested the hypothesis that our model's predictions for amplitude, timing, and frequency of S3 accurately predict the transthoracic phonocardiogram, using the simultaneously recorded transmitral Doppler E wave as input, in three subject groups: those with audible pathological S3, those with audible physiological S3, and those with inaudible S3. CONCLUSIONS: We found excellent agreement between model prediction and the observed data for all three subject groups. We conclude that, in the presence of a normal mitral valve, the kinematics of filling requires that all hearts have oscillations of the cardiohemic system during E-wave deceleration. However, the oscillations may not have high enough amplitude or frequency to be heard as an S3 unless there is sufficiently rapid fluid deceleration (of the Doppler E-wave contour) with sufficient cardiohemic coupling.

Adenosine use in pregnant women with supraventricular tachycardia.

OBJECTIVE: To review a case experience and published reports of treatment of supraventricular tachycardia with adenosine in pregnant women. DATA SOURCES: Published reports and clinical experience. DATA SYNTHESIS: Seven pregnant women with supraventricular tachycardia treated with adenosine have been described in the literature. We describe an eighth patient. Treatment has terminated the dysrhythmia in all cases, and no adverse maternal or fetal effects have been reported. CONCLUSIONS: Based on theoretical considerations and on limited published experience, adenosine appears to be safe and effective for treatment of supraventricular tachycardia in pregnant patients.

Pronounced metabolic response to modest theophylline overdose.

OBJECTIVE: To describe a patient who developed significant metabolic abnormalities in response to a low-level theophylline ingestion. CASE SUMMARY: An 18-year-old man was examined after ingesting theophylline 3 g in a suicide attempt. Although his peak theophylline concentration was 157 mumol/L (28.2 micrograms/mL), it was associated with significant leukocytosis, hypokalemia, hypomagnesemia, hypophosphatemia, hyperglycemia, and lactic acidosis. These abnormalities have been previously associated with theophylline intoxication, but only in conjunction with much higher peak concentrations of theophylline. CONCLUSIONS: Significant metabolic abnormalities can occur with suicidal ingestion of relatively small amounts of theophylline. The presence of these abnormalities should be sought in theophylline overdoses. In the proper clinical circumstances, such abnormalities should raise suspicion of covert theophylline ingestion.

Acute pericarditis with a symptomatic pericardial effusion complicating pregnancy. A case report.

A 30-year-old, white woman, gravida 4, para 2, abortus 1, was hospitalized at 21 weeks' gestation because of a symptomatic pericardial effusion. Extensive evaluation including pericardial biopsy failed to reveal a specific cause. Treatment with pericardiotomy and intrapericardial hydrocortisone was followed by relief of symptoms. The remainder of the pregnancy was uneventful. Idiopathic pericardial effusion in pregnancy is a rare problem, and the proper approach to evaluation and treatment is not known. We present an approach that resulted in a favorable outcome.

Bronchocentric granulomatosis, acute renal failure, and high titer antineutrophil cytoplasmic antibodies: possible variants of Wegener's granulomatosis.

We describe 2 patients with clinical syndromes suggestive of Wegener's granulomatosis: elevated titers of cytoplasmic antineutrophil cytoplasmic antibodies (cANCA), bronchocentric granulomatosis, and acute renal failure. A renal biopsy in one case showed crescentic glomerulonephritis and in the other case showed interstitial nephritis. These cases may reflect bronchocentric granulomatosis among a spectrum of diseases associated with cANCA. Use of cANCA may identify those patients with bronchocentric granulomatosis who require immunosuppressive therapy.

Hepatotoxicity associated with angiotensin-converting enzyme inhibitors.

OBJECTIVE: To review published reports of hepatotoxicity associated with angiotensin-converting enzyme (ACE) inhibitors and to explore possible mechanisms of injury. DATA SOURCES: Published reports of hepatotoxicity associated with use of ACE inhibitors and investigations that suggest potential mechanisms of injury. DATA SYNTHESIS: Nineteen cases of ACE-inhibitor-associated hepatotoxicity are presented. Early theories regarding mechanisms are reviewed. Laboratory investigations of hepatic effects of eicosanoids on hepatic function are reviewed and a novel mechanism by which ACE inhibitors may cause hepatic injury is postulated. CONCLUSIONS: Hepatotoxicity, usually cholestatic in nature, has been reported with captopril, enalapril, and lisinopril use. Apparent cross-reactivity has been reported twice. Potential mechanisms of injury include idiopathic hypersensitivity and modulation of eicosanoid metabolism by inhibition of kininase II and subsequent increased hepatic bradykinin activity. Mediation via altered eicosanoid metabolism provides a plausible explanation for cross-reactivity among ACE inhibitors. Hepatotoxicity resolves if ACE inhibitors are stopped but may progress to liver failure if treatment is continued.

Infectious and mechanical complications of central venous catheters placed by percutaneous venipuncture and over guidewires.

OBJECTIVE: To compare the frequency of infectious and mechanical complications of central venous and pulmonary artery catheters placed by initial venipuncture vs. over a guidewire at existing sites. HYPOTHESIS: Exchange of central venous catheters and pulmonary artery catheters over a guidewire as opposed to fresh venipuncture reduces mechanical complications without increasing risk of infection. DESIGN: Chart audit. PATIENTS: Medical, surgical, and coronary ICU patients requiring invasive monitoring or central venous access. INTERVENTIONS: Patients requiring prolonged catheterization underwent periodic exchange of catheters over a guidewire. Rates of catheter-related infections and mechanical complications were determined for central venous catheters placed by initial venipuncture and those catheters placed by guidewire exchange. MEASUREMENTS AND MAIN RESULTS: Over a 12-month period, 939 catheters were inserted in 454 patients. Of these 939 catheters, 534 were placed by guidewire exchange. Use of a guidewire was associated with a decreased frequency of pneumothorax and hemothorax compared with initial venipuncture (0/405 [0%] vs. 7/534 [1.3%], respectively; p < .05) but not with increased risk of infection (9/405 [2.2%] vs. 14/534 [2.6%], respectively; NS). Guidewire-facilitated replacement of multiple consecutive catheters at the same site did not increase the risk of catheter-related infection. Catheters placed via internal jugular veins were more likely to become infected than catheters placed via subclavian veins (17/477 [3.6%] vs. 3/430 [0.7%], respectively; p < .01). CONCLUSIONS: When prolonged central venous or pulmonary artery catheterization is necessary, periodic catheter replacement over a guidewire is associated with fewer mechanical complications than initial venipuncture. Periodic catheter replacement over a guidewire is also associated with no increase in risk of infection.

Decline in creatinine clearance in a patient with glomerulomegaly associated with a congenital cyanotic heart disease.

Glomerulomegaly is associated with congenital cyanotic heart disease and has heretofore been considered a benign condition. We describe a patient with congenital cyanotic heart disease and glomerulomegaly. Deterioration of renal function was demonstrated by comparison of creatinine clearances measured at the time of kidney biopsy and 4 years later. No alteration in kidney histology other than glomerulomegaly and focal glomerulosclerosis at autopsy could account for this deterioration. This is the first description of deterioration of renal function in a patient with glomerulomegaly and congenital cyanotic heart disease. This observation may influence the management of patients with glomerulomegaly and congenital cyanotic heart disease who are potential recipients of heart or heart-lung allografts.

Suspected cross-reactivity of enalapril- and captopril-induced hepatotoxicity.

OBJECTIVE: To present evidence that enalapril and captopril may produce hepatotoxicity by a common mechanism. DATA SOURCES: A case report and review of pertinent literature. DATA SYNTHESIS: A patient developed hepatotoxicity once while taking enalapril and again while taking captopril. Hepatotoxicity resolved with cessation of therapy. Hepatotoxicity has been reported with use of captopril, enalapril, and lisinopril. Apparent cross-reactivity has been reported on just one other occasion. CONCLUSIONS: Because hepatotoxicity is uncommon with angiotensin-converting enzyme (ACE) inhibitors, our observations suggest the possibility that these agents produce hepatotoxicity by a common mechanism. In patients who develop hepatotoxicity while taking one ACE inhibitor, other agents in this class probably should be avoided.

Hemolytic-uremic syndrome associated with ingestion of quinine.

Hemolytic-uremic syndrome following quinine ingestion is a newly described phenomenon, with just two previous descriptions of 4 cases in the literature. We describe a 5th case. The reaction may be mediated by the presence of antibodies reactive against platelets in the presence of quinine. Treatment has included use of plasma exchange, prednisone, aspirin, and dipyridamole. The patients have all regained some degree of renal function. However, it is unclear whether pharmacological treatment or spontaneous resolution is responsible for the improvement. Quinine-associated hemolytic-uremic syndrome probably occurs more often than is recognized. It is important to recognize this reaction when it occurs and to avoid further quinine exposure, since the reaction seems to be recurrent.

Peripartum cardiomyopathy.

We report a case of peripartum cardiomyopathy (PPCM) with a literature review. Although PPCM is an uncommon form of cardiomyopathy, it sometimes occurs in women of childbearing age and thus should be considered in a woman who develops heart failure in the peripartum period. The diagnosis is based on a compatible clinical picture and exclusion of other potential causes. Risk factors include being black, over 30 years old, and multiparous, as well as having preeclampsia or hypertension or a multiple birth. The cause is unknown but may be multifactorial. Treatment is similar to that for other dilated cardiomyopathies; steroids and immunosuppressive agents may be useful in some circumstances. Outcome is variable with a long-term survival rate of about 50%. Patients who survive usually have few symptoms.