Howard Willens

Relationship of peripheral arterial compliance and standard cardiovascular risk factors.

Abnormalities of peripheral arterial compliance are clinically useful markers of atherosclerosis and risk of vascular events. Local peripheral arterial compliance can be easily and accurately assessed in the clinic by computer-controlled pulse volume recordings (air plethysmography). The purpose of this study was to investigate the relationship between clinical cardiovascular risk factors, a surrogate of atherosclerotic burden, and peripheral arterial compliance in the thigh and calf determined by quantification of local pulse volume recordings in patients undergoing coronary angiography. Peripheral arterial compliance in the thigh and calf was measured in 346 patients undergoing diagnostic cardiac catheterization at 4 centers. Demographic and cardiovascular risk factor data were collected, and their relationship to local arterial compliance examined using a new device that assesses maximal local arterial volume change in an extremity segment. Pulse volume recordings detected decreased local arterial compliance in the thigh associated with a history of hypertension (p< 0.0001), diabetes mellitus (p = 0.0001), and hyperlipidemia (p = 0.0007). In the calf, this arterial compliance measure was associated with a history of hypertension (p < 0.0001) and diabetes mellitus (p = 0.002). Females had lower arterial compliance than males in the thigh (p = 0.003) and calf (p <0.0001). Limited evidence of lower arterial compliance in the thigh was found for those with obesity (p = 0.07). This procedure also demonstrated that subjects with multiple cardiovascular risk factors had lower arterial compliance in the thigh than subjects with no or 1 risk factor (p = 0.0001). Peripheral arterial compliance determined by air plethysmography is strongly associated with standard cardiovascular risk factors. The noninvasive measurement of local arterial compliance by regional pulse volume recording may be a useful adjunct for cardiovascular risk stratification early in the course of the disease as well as for monitoring vascular response to therapy.

Ankle/Brachial Index in the Primary Care Setting

Peripheral arterial disease (PAD) is an underdiagnosed circulatory problem in the primary care setting. Individuals are at increased risk for cardiovascular disease; therefore, there is the need for a technique capable of early identification and detection of patients with PAD. The focus of this study was to compare the accuracy of a new operator-independent method of measuring ankle brachial index (ABI) with the traditional Doppler ultrasound method of determining ABI. In 246 limbs the authors compared ankle systolic pressures and ABI measured by a new automated oscillatory method called the ABIgram with those measured by standard Doppler ultrasound. In phase 1, the 2 methods for measuring ankle systolic pressure had a mean difference of 2 mm Hg with a standard deviation of 6.7 mm Hg. In phase 2 the mean difference was 3.1 mm Hg with a standard deviation of 5.1 mm Hg. Further, ABI as measured by the 2 methods fell within 1% and demonstrated a 5% error in reproducibility. These numbers pass the SP-10 standard for medical devices established by the FDA. The ABIgram module of the Vasocor ®Vascular Diagnostic Center offers primary care physicians the ability to rapidly obtain ABI measurements comparable to the standard technique. Further, the ABIgram may be operated by staff commonly found in the primary care setting.

Studies on the possible mechanisms of lidoflazine arrhythmogenicity

Lidoflazine is a calcium channel blocking agent that is effective and safe in the treatment of angina pectoris, but has been reported to be associated with sudden death when administered for the treatment of supraventricular arrhythmias. Studies were performed in dogs to determine if lidoflazine caused a rise in serum digoxin concentration that could cause arrhythmias or if it was directly arrhythmogenic. Dogs received chronic injections of digoxin and then digoxin in combination with lidoflazine. No increase in digoxin concentration was found. Dogs also underwent programmed electrical stimulation while not receiving medications and then after incremental doses of lidoflazine administered intravenously. Lidoflazine did not cause spontaneous ventricular tachycardia and did not lower the threshold of ventricular tachycardia induction. Combined administration of lidoflazine and digoxin did not facilitate arrhythmia induction. These studies do not support a digoxin-lidoflazine interaction or a direct arrhythmogenic action of lidoflazine.

Correlation of peripheral arterial compliance and Framingham coronary heart disease risk evaluation

An office-based air plethysmograph, with internal calibration (VasogramTM), was used to measure arterial compliance (AV/AP) at the thigh and calf in a 4 center clinical study, with 342 subjects (males aged 31 to 69 and females aged 41 lo 79). The subjects were stratified into 4 groups according to Framingham Cardiovascular Risk with 38-47 subjects in each gender/risk group. Group 1. Risk 20% or coronary equivalence but no documented coronary artery disease (CAD). Group 4. documented CAD. Arterial compliance was measured at the thigh and calf levels on each subject, on three different occasions, over a four-week period. Compliance was reported as the maximum volume change (ml) under the cuff occurring during a single cardiac cycle, normahzed lo a pulse pressure of 50 mmHg (MaxV50) with mean levels summarized in the table below: POSTER SESSION 1104 Platelets, Endothelium, and Thrombosis I

Lidoflazine and propranolol combination treatment in chronic stable angina.

The short-term (1 month) and long-term (6 months) safety of combination lidoflazine-propranolol therapy was investigated in an open trial of 15 patients with stable angina of effort. The possible advantages of adding lidoflazine (ti trated to 360 mg daily) to patients having a therapeutic response to propranolol (80-400 mg daily) was also evaluated. Effects on non-invasive indexes of left ventricular function (echocardiography, systolic time intervals, radionuclide ventriculography) and exercise tolerance (treadmill exercise testing) were deter mined. There was no change in mean resting heart rate with the combination therapy, although one patient developed sinus bradycardia at a rate of 44 and had to have his propranolol dose reduced. Electrocardiographic analysis showed significant prolongation of the QTc intervals on lidoflazine-propranolol therapy compared to propranolol alone, with 3 patients having QTc interval prolongation to above .53 seconds, but there was no evidence of increased ar rhythmogenesis with the combination therapy compared to propranolol alone. Left ventricular end-diastolic volume index tended to rise with combination therapy. However, lidoflazine-propranolol therapy did not produce any signifi cant effects on resting ejection fraction determined by M-mode echocardio graphy or by radionuclide ventriculography. Radionuclide ventriculography determined peak exercise ejection fractions were also not significantly changed with combination therapy compared to propranolol alone. There were only small, insignificant improvements in exercise tolerance with the lidoflazine-pro pranolol combination treatment compared to propranolol alone. It is concluded that lidoflazine-propranolol combination therapy is generally safe but has the potential of causing serious adverse effects in certain patients, i.e. those with sick sinus disease, prolonged QTc intervals, and severe baseline left ventricular dysfunction, and that caution must be exercised in its use. Furthermore, it would appear that combination therapy provides only slight, if any, improve ments in exercise tolerance in patients with chronic stable angina having a ther apeutic response to oral propranolol.

Comparison of noninvasive arrhythmia induction techniques with electrophysiologic studies and evaluation of lorcainide in patients with symptomatic ventricular tachycardia

Twenty-six patients (19 men and 7 women) with symptomatic ventricular tachycardia (VT) were studied using invasive and noninvasive techniques to induce VT. Of the study population, 12% had syncope and VT on Holter monitoring, 30% had cardiac arrest and 58% had symptomatic VT. All patients had antiarrhythmic agents stopped 5 half-lives before evaluation and then had autonomic profile (upright tilt, cold pressor test, exercise testing and hand grip) as well as programmed electrical stimulation studies performed. Autonomic profile testing induced VT in 5 of 26 patients (19%) and in only 1 patient was the arrhythmia reproducibly induced. All 26 patients had VT induced on electrophysiologic testing; 9 patients had nonsustained and 17 had sustained VT. Lorcainide administered intravenously prevented VT induction in 20 of 26 patients tested, whereas procainamide was effective in 11 of 24 patients. Ten of the 13 not protected by procainamide were protected by lorcainide. Twenty patients were started on long-term lorcainide therapy and followed up for 29 +/- 3.4 months. Five patients have discontinued therapy, 2 because of breakthrough arrhythmias, 2 because of severe sleep-wake disturbances and 1 because of private physician preference. An additional 3 patients died during therapy because of myocardial infarction in 1, progressive myopathy in 1 and sudden death in 1. Sixty percent of patients started on lorcainide therapy have continued. In this patient population, noninvasive induction of VT is not a sensitive or reproducible technique in assessing antiarrhythmic therapy. Furthermore, when selected on the basis of electrophysiologic testing, lorcainide is a well-tolerated and effective antiarrhythmic agent.