Sanjay Tyagi

Phosphodiesterase-5 Inhibitor in Eisenmenger Syndrome A Preliminary Observational Study

Background— Phosphodiesterase-5 inhibitors produce a significant decrease in pulmonary vascular resistance in patients with idiopathic pulmonary arterial hypertension. We studied the effects of tadalafil, a phosphodiesterase-5 inhibitor, on short-term hemodynamics, tolerability, and efficacy over a 12-week period in patients of Eisenmenger syndrome having a pulmonary vascular pathology similar to idiopathic pulmonary arterial hypertension. Methods and Results— Sixteen symptomatic Eisenmenger syndrome patients (mean age, 25±8.9 years) were assessed hemodynamically at baseline and 90 minutes after a single dose of tadalafil (1 mg/kg body weight up to a maximum of 40 mg). The same dose was then continued daily for 12 weeks, and the patients were restudied. There was a significant decrease in mean pulmonary vascular resistance immediately (24.75±8.49 to 19.22±8.23 Woods units; P<0.005) and at 12 weeks (19.22±8.23 to 17.02±6.19 Woods units; P=0.03 versus 90 minutes). Thirteen of 16 patients (81.25%) showed a ≥20% decrease in pulmonary vascular resistance and were defined as responders. The mean systemic oxygen saturation improved significantly both immediately (84.34±5.47% to 87.39±4.34%; P<0.005) and at 12 weeks (87.39±4.34% to 89.16±3.8%; P<0.02 versus 90 minutes) without a significant change in systemic vascular resistance. None of the patients had a fall in systemic arterial pressure, worsening of systemic oxygen saturation, or any adverse reactions to the drug. The mean World Health Organization functional class improved from 2.31±0.47 to 1.25±0.44 (P<0.0001), and the 6-minute walk distance improved from 344.56±119.06 to 387.56±117.18 m (P<0.001). Conclusions— Preliminary evaluation of tadalafil has shown efficacy and safety in selected patients with Eisenmenger syndrome, warranting further investigation in this subgroup of patients.

Early and long-term results of subclavian angioplasty in aortoarteritis (Takayasu disease): comparison with atherosclerosis.

AbstractPurpose: To compare the early and long-term outcomes of subclavian artery angioplasty in patients with aortoarteritis and atherosclerosis.n Methods: Sixty-one subclavian artery angioplasties were performed in 55 consecutive patients with aortoarteritis (n=32) and atherosclerosis (n=23) between 1986 and 1995. An arch aortogram followed by a selective subclavian artery angiogram was done to profile the site and extent of the lesion, its relation to the vertebral artery, and the distal circulation. Percutaneous transluminal angioplasty (PTA) was performed via the femoral route for 56 stenotic lesions and 5 total occlusions.n Results: PTA was successful in 52 (92.8%) stenotic lesions and 3 (60%) total occlusions. Three patients (5.4%) had complications, that could be effectively managed nonsurgically. Compared with atherosclerosis, patients with aortoarteritis were younger (27.4±9.3 years vs 54.5±10.5 years; p<0.001), more often female (75% vs 17.4%; p<0.001), gangrene was uncommon (0% vs 17.4%; p<0.05), and diffuse involvement was seen more often (43.8% vs 4.4%; p<0.001). The luminal diameter stenoses were similar before PTA (88.6±9.7% vs 89.0±9.1%; p=NS). Higher balloon inflation pressure was required to dilate the lesions of aortoarteritis (9.9±4.6 ATM vs 5.5±1.0 ATM; p<0.001). This group had more residual stenosis (15.5±12.4% vs 8.3±9.4%; p<0.05) after PTA. There were no neurological sequelae, even in PTA of prevertebral lesions. On 3–120 months (mean 43.3±28.9 months) follow-up of 40 patients, restenosis was more often observed in patients with aortoarteritis, particularly in those with diffuse arterial narrowing. These lesions could be effectively redilated. Clinical symptoms showed marked improvement after successful angioplasty.n Conclusion: Subclavian PTA is safe and can be performed as effectively in aortoarteritis as in atherosclerosis, with good long-term results. Long-term follow-up shows that it provides good symptomatic relief.

Balloon angioplasty for renovascular hypertension in Takayasu's arteritis

Percutaneous transluminal renal angioplasty was performed in 54 consecutive patients with hypertension and renal artery stenosis caused by Takayasus arteritis. Angioplasty was technically successful in 67 (89.3%) of 75 lesions attempted. In these 67 lesions, the degree of stenosis decreased from 88.3 +/- 4.8% to 23.5% +/- 13.6% (p < 0.001) after angioplasty. Following successful angioplasty there was significant improvement in hypertension (p < 0.001) within 48 hours. Patients with bilateral renal artery stenosis had higher systolic blood pressure both before balloon dilatation (p < 0.05) and after balloon dilatation before discharge (p < 0.001), compared with patients with unilateral renal artery stenosis. Three to 70 months (mean 26.4 +/- 10.3 months) after successful angioplasty, blood pressure was reduced to normal or was improved in 93% of patients. Angiographic restudy an average of 14.2 +/- 7.8 months after angioplasty showed restenosis at the same site in 7 of 52 (13.5%) lesions and fresh stenosis in one artery. All these eight lesions were successfully dilated. Further improvement in the luminal diameter was observed in 11 (21.2%) lesions. Late angiographic restudy in seven patients an average of 56.1 +/- 6.3 months after angioplasty showed no restenosis. Our results suggest that balloon angioplasty is safe and highly effective in relieving renal artery stenosis caused by Takayasus arteritis and should be the treatment of choice for renovascular hypertension in this disease.

Balloon angioplasty of native coarctation of the aorta in adolescents and young adults

Balloon angioplasty of native coarctation of the aorta was performed in 35 consecutive adolescents and young adults, aged 14 to 37 years (mean 22.6 +/- 7.1). Twenty-eight (80%) patients had isolated discrete coarctation, six (17.1%) had tubular hypoplasia of the aortic isthmus, and one (2.9%) had hypoplasia of the post-coarctation aorta. The peak systolic pressure gradient decreased from 78.5 +/- 23.9 to 15.7 +/- 11.6 mm Hg (p less than 0.001), and the mean coarctation diameter increased from 4.7 +/- 2.4 to 13.1 +/- 2.7 mm (p less than 0.001) immediately after angioplasty. Patients with discrete-type coarctation had significantly less residual gradient than patients with long-segment tubular coarctation (12.3 +/- 10.7 vs 27.2 +/- 6.6 mm Hg, p less than 0.01). On recatheterization and angiography in 26 patients at 12.6 +/- 1.5 months after dilatation, there was no significant change in gradient (15.5 +/- 13.3 mm Hg) and diameter (13.1 +/- 1.8 mm) from the immediate post-angioplasty results. However, two patients had an increase in gradient and three had small aortic aneurysms with no change in appearance on restudy after 2 years. After 3 to 67 months (mean 32.7 +/- 19.2) follow-up, all patients showed continued clinical improvement. Hypertension was relieved in 37.5% (12/32) and improved in 59.4% (19/32). Our experience suggests that balloon angioplasty of native aortic coarctation in adolescents and young adults is safe and highly effective with sustained improvement on intermediate-term follow-up.

Balloon angioplasty of the aorta in Takayasu's arteritis : initial and long-term results

Percutaneous transluminal balloon angioplasty for stenosis of the aorta was performed in 36 patients with Takayasus arteritis (age range, 8 to 36 years; mean, 19.1 +/- 7.7 years). Balloon dilatation was successful in 34 patients and resulted in a decrease in the mean peak systolic pressure gradient (PSG) from 75.2 +/- 29.1 mm Hg to 24.8 +/- 19 mm Hg (p less than 0.001) and a mean increase in the diameter of the stenosed segments from 4.5 +/- 2.2 mm to 9.6 +/- 3.8 mm (p less than 0.001). Hemodynamic and angiographic restudy, which was performed in 20 patients at a mean follow-up period of 7.7 +/- 4.1 months (range, 3 to 24 months), showed a further decrease in PSG (greater than or equal to 15 mm Hg) in seven patients (from 40.0 +/- 11.2 mm Hg to 15.7 +/- 10.2 mm Hg; p less than 0.01), no significant change in PSG in 12 patients (17.1 +/- 13.6 mm Hg vs 16.6 +/- 12.7 mm Hg; p = NS), and an increase in PSG from 15 mm Hg to 85 mm Hg in one patient. The patient who showed restenosis underwent successful redilatation. Six patients who underwent late recatheterization and angiography at 36 to 60 months (mean, 43 +/- 9.4 months) show continued relief of stenosis (mean PSG, 8.8 +/- 7.8 mm Hg). Patients with short-segment (less than 4 cm) stenosis experience more relief than patients with long-segment (greater than or equal to 4 cm) stenosis (residual PSG, 18.6 +/- 8.2 mm Hg vs 40 +/- 16 mm Hg; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

SELF- AND BALLOON-EXPANDABLE STENT IMPLANTATION FOR SEVERE NATIVE COARCTATION OF AORTA IN ADULTS

BACKGROUNDnBalloon angioplasty for native coarctation of the aorta (CoA) in adults, though promising, is sometimes limited by significant residual gradient (>20 mm Hg). Few studies available have reported on use of balloon-expandable stents in such a situation. We evaluated the use of self- and balloon-expandable stents in patients with suboptimal response to balloon angioplasty (BA).nnnMETHODSnTwenty-one hypertensive patients (age, 18 to 61 years; mean, 28.6 +/- 11.2 years) with native CoA and in whom results of BA were suboptimal (ie, residual peak systolic gradient [PSG] >20 mm Hg) underwent stent implantation. Balloon-expandable Palmaz stents were implanted in 5 patients (group A) and self-expandable nitinol aortic stents in the remaining 16 patients (group B).nnnRESULTSnIn group A, PSG decreased from 62.8 +/- 10.6 (53 to 80) mm Hg to 28.1 +/- 6.3 (22 to 39) mm Hg after BA. Systolic gradient further decreased to 8.3 +/- 3.9 (2 to 16) mm Hg (P <.001) after implantation of the balloon-expandable Palmaz stent. In group B, PSG decreased from 70.2 +/- 24.6 (40 to 110) mm Hg to 28.4 +/- 9.8 (22 to 42) mm Hg after BA and further reduced to 9.0 +/- 5.5 (4 to 16) mm Hg (P <.001). One of these patients had a nitinol self-expandable stent implanted after a Palmaz stent embolized immediately after deployment. Nitinol stents were easier to deploy and conformed better to aortic anatomy compared with balloon-expandable stents. In group A, the diameter of the coarcted segment increased from 3.8 +/- 0.8 mm to 13.3 +/- 0.8 mm (P <.001) after stent implantation and in group B it increased from 4.5 +/- 1.1 mm to 14.1 +/- 2.1 mm (P <.001). There was no significant difference between the two groups in the PSG and diameter of the coarcted segment before and after stent implantation. With the exception of one case, in which a Palmaz stent embolized, there was no other complication in our series. On follow-up of 12 to 71 months (mean, 40.7 +/- 5.8 months) all the implanted stents remained in their original position and none showed evidence of fracture. Improvement in hypertension was seen in 20 of 21(95.2%) of the patients. On recatheterization and angiography 1.2 +/- 0.6 years after implantation in 19 patients, one patient showed an increase in PSG to 27 mm Hg across the nitinol stent and underwent successful redilation. No increase in gradient was seen in other patients. Beneficial late remodeling was seen in 10 of 14(71.4%) of patients restudied after implantation of self-expandable stent. None of the patients showed aneurysm formation.nnnCONCLUSIONSnStent implantation is safe and effective in improving suboptimal results after BA for CoA. Self-expandable stents were easier to implant, adapted better to the wall of the aorta, and in most patients had similar efficacy in reducing coarctation as balloon-expandable stents.

Long-term results after balloon pulmonary valvuloplasty in adults

Percutaneous balloon pulmonary valvuloplasty for congenital pulmonary valve stenosis was performed in 40 adult patients (aged 18 to 56 years). The duration of follow-up was 24.5 +/- 11.5 months. The peak systolic pressure gradient from the right ventricle to the pulmonary artery decreased from 107 +/- 29 mm Hg to 37 +/- 25 mm Hg immediately after the procedure. On follow-up, gradient obtained either by cardiac catheterization or Doppler echocardiography was 31 +/- 13 mm Hg. In eight patients with residual gradient after valvuloplasty of > 50 mm, the mean peak systolic gradient decreased from 74.5 +/- 18.3 to 33.5 +/- 13.9 mm Hg on follow-up. Thus balloon pulmonary valvuloplasty is a safe and effective procedure for the treatment of adult patients with pulmonic stenosis; there is a tendency for high residual gradients to regress on follow-up.

Clinical efficacy of phosphodiesterase-5 inhibitor tadalafil in Eisenmenger syndrome--a randomized, placebo-controlled, double-blind crossover study.

OBJECTIVESnIn a randomized double-blind crossover trial, we compared the efficacy of phosphodiesterase-5 (PDE-5) inhibitor tadalafil with placebo in patients of Eisenmenger Syndrome (ES). The primary end point was the change in 6-minute walk test distance (6 MWD). Secondary end points were the effect of the drug on systemic oxygen saturation (SO(2) ), pulmonary vascular resistance (PVR), systemic vascular resistance (SVR), effective pulmonary blood flow (EPBF), and World Health Organization (WHO) functional class.nnnBACKGROUNDnES is a disorder with limited treatment options. Uncontrolled studies have shown PDE-5 inhibitors to be beneficial in patients of ES.nnnMETHODSnTwenty-eight symptomatic adult patients of ES with weight ≥30u2003kg in WHO class II and III were enrolled. Patients were given 40 mg of tadalafil or matching placebo for 6 weeks followed by crossover to the other drug after a washout period of 2 weeks. Assessment of WHO class, exercise capacity by 6 MWD, and various hemodynamic parameters by cardiac catheterization was done at baseline, after 6 weeks and at the end of the study.nnnRESULTSnAll patients completed the study. There was significant increase in 6 MWD following drug administration compared with baseline (404.18 ± 69.54 m vs. 357.75 ± 73.25u2003m, P < .001). Compared with placebo, tadalafil produced significant decrease in PVR (-7.32 ± 1.58, P < .001), resulting in significant increase in EPBF (0.12 ± 0.05, P= .03), SO(2) % (1.72 ± 0.58, P= .007), and WHO functional class (1.96 ± 0.18 vs. 2.14 ± 0.44, P= .025), with no significant change in SVR (P= NS).nnnCONCLUSIONnIn this first short-term placebo-controlled trial of tadalafil in patients of ES, the drug was well tolerated and significantly improved exercise capacity, functional class, SO(2) , and pulmonary hemodynamics.

Percutaneous transluminal balloon angioplasty of the aorta in patients with aortitis.

Four patients with aortitis and stenotic lesions of the aorta were successfully treated by percutaneous transluminal balloon angioplasty. The peak systolic gradient across the constrictions decreased from 82.5 +/- 35.7 to 37.5 +/- 18.5 mm Hg immediately after dilatation. Repeat angiography in the first three patients performed 2 months later showed a further decrease in the gradient to 13.8 +/- 9.5 mm Hg. There were no complications during or after the procedure, and all the patients have shown remarkable symptomatic relief during the follow-up.

Pentoxifylline Therapy for Hepatopulmonary Syndrome: A Pilot Study

H epatopulmonary syndrome (HPS) is characterized by a triad of liver disease, hypoxemia, and intrapulmonary vascular dilations (IPVDs). Its prevalence is 4% to 47% in patients with cirrhosis. Patients with HPS demonstrate a significant reduction in exercise capacity due to abnormal pulmonary circulation. Anatomic arteriovenous shunts in the lung are used during exercise and lead to exercise-induced impairment in gas exchange and exercise-induced arterial hypoxemia. The pathogenesis of HPS is unclear. Cytokinemediated injury is alleged to play a key role. Endothelin-1 and tumor necrosis factor (TNF) interaction, occurring in the lung vasculature, contribute to the development of experimental HPS. Overproduction of TNF, due to endotoxin stimulation of Kupffer cells, might be a major mechanism leading to HPS. Pentoxifylline, a nonspecific phosphodiesterase-4 inhibitor, blocks TNF synthesis and TNF-induced macrophagic nitric oxide production. Pentoxifylline prevented the development of HPS and attenuated HPS in cirrhotic rats. However, to our knowledge, pentoxifylline has not been used clinically for the treatment of HPS. In this study, we tried pentoxifylline therapy in patients with HPS.