Thomas J. Waltman

Utility of Right Ventricular Tei Index in the Noninvasive Evaluation of Chronic Thromboembolic Pulmonary Hypertension Before and After Pulmonary Thromboendarterectomy

OBJECTIVES We evaluated the utility of tissue Doppler-derived right ventricular (RV) Tei (or myocardial performance) index in patients with chronic thromboembolic pulmonary hypertension (CTEPH) before and after pulmonary thromboendarterectomy (PTE) and assessed correlations with mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and cardiac output (CO). BACKGROUND The assessment of RV function is limited with 2-dimensional echocardiography. The RV Tei index, an indicator of RV myocardial performance, is derived by Doppler measurements and is unaffected by RV geometry. The use of tissue Doppler imaging (at the lateral tricuspid annulus) for RV Tei index calculation is simple and eliminates the need for pulsed-wave Doppler recordings of both RV inflow and outflow. METHODS Ninety-three patients with CTEPH were prospectively studied along with 13 control patients. Right ventricular tissue Doppler imaging and right heart catheterization were performed before and after PTE. Right ventricular Tei index was compared with values of mPAP, PVR, and CO with the use of linear regression. RESULTS Right ventricular Tei index was 0.52 +/- 0.19 in patients with CTEPH and 0.27 +/- 0.09 in control patients (p < 0.0001). After PTE, RV Tei index decreased to 0.33 +/- 0.10 (p < 0.0001). Pulmonary vascular resistance correlated well with RV Tei index before (r = 0.78, p < 0.0001) and after (r = 0.67, p < 0.0001) surgery. Also, the absolute change in Tei index in each patient after PTE correlated well with the concomitant change in PVR (r = 0.75, p < 0.0001). RV Tei index did not correlate as well with mPAP (pre-operatively: r = 0.55, p < 0.0001; post-operatively: r = 0.26, p = 0.03) or CO (pre-operatively: r = 0.57, p < 0.0001; post-operatively: r = 0.43, p < 0.0001). CONCLUSIONS These results demonstrate a correlation between RV Tei index and right heart hemodynamics (particularly PVR) in CTEPH. Because PVR is difficult to estimate noninvasively -- and yet correlates with disease severity -- the RV Tei index may be a valuable noninvasive parameter for monitoring disease severity in CTEPH and outcome after PTE.

Effect of prolonged catecholamine infusion on immunoregulatory function: Implications in congestive heart failure

OBJECTIVES This study sought to characterize the effects of prolonged catecholamine infusion on immunoregulatory cell traffic and activation. BACKGROUND Immunoregulation has been shown to be partially controlled by the sympathetic nervous system. Although short-term elevation of catecholamine levels is known to alter immunoregulatory cell traffic and activation, the effects of prolonged heightened sympathetic nervous system activity have not adequately been studied. We believe that the alterations in immune function seen in patients with congestive heart failure are linked to a prolonged elevation of circulating catecholamine levels. METHODS To characterize the effects of prolonged elevation of catecholamine levels, rats received 4 weeks of constant infusion of epinephrine or norepinephrine through implanted osmotic minipumps. Peripheral and splenic leukocyte subsets, T cell proliferation and interleukin-2 receptor expression were quantified. Antibody production to the novel antigen keyhole limpet hemocyanin was assessed over the 4-week treatment period. RESULTS Both epinephrine and norepinephrine caused significant splenic atrophy and cardiac hypertrophy; both were blocked by propranolol. Epinephrine induced lymphocytosis; both catecholamines caused an increase in natural killer cells. In the spleen, both epinephrine and norepinephrine led to a dose-dependent decrease in total T cells, suppressor/cytotoxic T cells and natural killer cells and a significant increase in B cells. Epinephrine at the low dose enhanced mitogen-induced proliferation and interleukin-2 receptor expression. Norepinephrine at the low dose appeared to diminish proliferation. Epinephrine tended to inhibit IgG antibody production, whereas norepinephrine had no effect. CONCLUSIONS The results of our study indicate that prolonged elevation of catecholamine levels alters immune cell proliferation and differentiation. These alterations differ greatly from those induced by short-term stimulation but, for the most part, parallel those found in patients with congestive heart failure. We postulate that the shifts in immunoregulatory cell type and function seen in patients with congestive heart failure are due, in part, to longstanding increases in circulating catecholamine levels and may play an important role in the pathogenesis and progression of disease.

Left ventricular strain and strain rate by 2D speckle tracking in chronic thromboembolic pulmonary hypertension before and after pulmonary thromboendarterectomy

BackgroundEchocardiographic evaluation of left ventricular (LV) strain and strain rate (SR) by 2D speckle tracking may be useful tools to assess chronic thromboembolic pulmonary hypertension (CTEPH) severity as well as response to successful pulmonary thromboendarterectomy (PTE).MethodsWe evaluated 30 patients with CTEPH before and after PTE using 2D speckle tracking measurements of LV radial and circumferential strain and SR in the short axis, and correlated the data with right heart catheterization (RHC).ResultsPTE resulted in a decrease in mean PA pressure (44 ± 15 to 29 ± 9 mmHg), decrease in PVR (950 ± 550 to 31 ± 160 [dyne-sec]/cm5), and an increase in cardiac output (3.9 ± 1.0 to 5.0 ± 1.0 L/min, p < 0.001 for all). Circumferential and posterior wall radial strain changed by -11% and +15% respectively (p < 0.001 for both). Circumferential SR and posterior wall radial SR changed by -7% and 6% after PTE. While the increase in posterior wall SR with PTE reached statistical significance (p = 0.04) circumferential SR did not (p = 0.07). In addition, septal radial strain and SR did not change significantly after PTE (p = 0.1 and 0.8 respectively). Linear regression analyses of circumferential and posterior wall radial strain and SR revealed little correlation between strain/SR measurements and PVR, mean PA pressure, or cardiac output. However, change in circumferential strain and change in posterior wall radial strain correlated moderately well with changes in PVR, mean PA pressure and cardiac output (r = 0.69, 0.76, and 0.51 for circumferential strain [p < 0.001 for all] and r = 0.7, 0.7, 0.45 for posterior wall radial strain [p = 0.001, 0.001, and 0.02, respectively]).ConclusionsLV circumferential and posterior wall radial strain change after relief of pulmonary arterial obstruction in patients with CTEPH, and these improvements occur rapidly. These changes in LV strain may reflect effects from improved LV diastolic filling, and may be useful non-invasive markers of successful PTE.

Effects of enalapril on T and B cell function in rats after myocardial infarction

The cellular mechanisms following myocardial infarction remain poorly characterized. It is believed that an inflammatory and immunologic process may be involved and that the beneficial effects of enalapril on remodeling may, in part, work through an immune mechanism. To characterize the effect of enalapril on immune alterations in the late phase of ventricular remodeling after myocardial infarction, rats underwent left coronary artery ligation followed by 6 weeks of either enalapril or placebo treatment. Infarct sizes, heart weights, and volumes were compared. Peripheral and splenic leukocyte and lymphocyte subsets, along with T cell blastogenesis, were quantified in enalapril treated rats 6 weeks after coronary ligation and compared to untreated control rats. Additionally, antibody production to a de novo antigen, keyhole limpet hemocyanin, was assessed with and without treatment. Average infarct size was equivalent among enalapril-treated myocardial infarction rats and untreated infarct rats. There was, however, less left and right ventricular hypertrophy in the enalapril treated group. Enalapril completely prevented the 42% increase in white blood count, the 88% increase in neutrophils, and the 28% increase in lymphocyte count seen in untreated infarct rats. Both untreated and enalapril treated rats tended toward a decrease in T helper:suppressor ratio. All rats treated with enalapril, however, had a significant increase in the T helper:suppressor ratio versus untreated control rats (F = 3.6, P = .018). Blastogenesis was markedly increased in T cells from infarcted animals. This was mitigated by treatment with enalapril. Additionally, immunoglobulin G antibody production was significantly lessened in rats treated with enalapril. The results of this study suggest that alterations in immunoregulatory cell type and function occurs following myocardial infarction. The beneficial effects of the angiotensin-converting enzyme inhibitor enalapril may be, in part, due to its mitigating effects on immune cell release and activation following myocardial infarction.

Rapid progression of common femoral artery stenosis leading to development of ischemic foot ulcer following repeated ipsilateral arterial access

Common femoral artery stenosis is well appreciated in patients with peripheral arterial disease, but not described following repeated arterial access. We present a case of progressive right common femoral artery stenosis resulting in resting leg ischemia and ulceration that was temporally related to multiple ipsilateral vascular access procedures for recurrent coronary and peripheral diagnostic and therapeutic procedures. We hypothesize that recurrent arterial injury in a setting of diabetes resulted in progressive critical common femoral artery stenosis.

RIGHT VENTRICULAR CARDIAC POWER OUTPUT IS INVERSELY RELATED TO PULMONARY VASCULAR RESISTANCE IN CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION

Studies have shown that left ventricular cardiac power output (CPO) is a measure of global cardiac function and a predictor of cardiogenic shock mortality. The utility of right ventricular (RV) CPO, however, is unclear. Our aim was to investigate RV CPO in patients with chronic thromboembolic