Diastolic and systolic right ventricular dysfunction precedes left ventricular dysfunction in patients paced from right ventricular apex.

BACKGROUND: Cardiac dysfunction after right ventricular (RV) apical pacing is well known but its extent, time frame of appearance and individual effect on left ventricular (LV), RV systolic and diastolic parameters has not evaluated in a systematic fashion. METHODS: Patients with symptomatic bradycardia and ACC-AHA Class I indication for permanent pacemaker implantation (PPI) were implanted a single chamber (VVI) pacemaker. They were followed prospectively by echocardiographic examination which was done at baseline, 1 week, 1 month and 6 months after implantation. Parameters observed were chamber dimensions (M-line), chamber volumes, cardiac output (modified Simpson's method), systolic functions (ejection fraction, pre-ejection period, ejection time and ratio) and diastolic functions( isovolumic relaxation time & deceleration time) of left and right heart. RESULTS: Forty eight consecutive patients (mean age 65.6+/-11.8 yrs, 66.7% males, mean EF 61.82+/-10.36%) implanted a VVI pacemaker were enrolled in this study. The first significant change to appear in cardiac function after VVI pacing was in diastolic properties of RV as shown by increase in RV isovolumic relaxation time (IVRT) from 65.89+/-15.93 to 76.58+/-17.00 ms,(p<0.001) at 1week and RV deceleration time (DT) from 133.84+/-38.13 to 153.09+/-31.41 ms, (p=0.02) at 1 month. Increase in RV internal dimension (RVID) from 1.26+/-0.41 to 1.44+/-0.44, (p<0.05) was also noticed at 1 week. The LV diastolic parameters were significantly altered after 1 month with increase in LV-IVRT from 92.36+/-21.47 to 117.24+/-27.21ms, (p<0.001) and increase in LV DT from 147.56+/-31.84 to 189.27+/-28.49ms,(p<0.01). This was followed by LV systolic abnormality which appeared at 6 months with an increase in LVPEP from 100.33+/-14.43 to 118.41+/-21.34ms, (p<0.001) and increase in LVPEP/LVET ratio from 0.34+/-0.46 to 0.44+/-0.10, (p<0.001)]. The reduction in LV EF was manifested at 6 months falling from 61.82+/-10.36% to52.52+/-12.11%, (p<0.05) without any significant change in the resting cardiac output. CONCLUSION: The present study shows that dysfunction of right ventricle is the first abnormality that occurs in VVI paced patients, which manifests by 1 week followed by LV dysfunction which starts appearing by 1 month and the diastolic dysfunctions precede the systolic dysfunction in both ventricles.

Amphotericin B lipid complex in the management of antimony unresponsive Indian visceral leishmaniasis.

Fifty-eight Indian patients with visceral leishmaniasis who did not respond or relapsed after 30 days of consecutive sodium stibogluconate therapy were randomised to treatment with amphotericin B lipid complex (ABLC) using a total dose of 7.5 or 10 mg/kg. Treatment induced a prompt clinical response in all patients with resolution of fever and regression in spleen size. Fever and chills developed during ABLC infusion, but it diminished with successive infusions. Fourteen days after treatment, 26 of 28 (93%) patients in the 7.5 mg/kg group and all 30 (100%) in the 10 mg/kg group had splenic aspirate parasite density scores of 0 and were considered apparent clinical and parasitologic responders. Four and three patients in the 7.5 and 10 mg/kg groups respectively relapsed during six months of followup; thus, overall 22 of 28 (79%) patients treated with 7.5 mg/kg and 27 of 30 (90%) treated with 10 mg/kg were definitive cures. All initial non-responders and relapses were retreated successfully with higher dose of ABLC. These results confirm the efficacy of short-course ABLC therapy for antimony-unresponsive Indian patients with visceral leishmaniasis. Since treatment with a total dose of 7.5 mg/kg did not appear to increase efficacy (79% vs. 84% induced by 5 mg/kg in a prior study), initial treatment with a total dose of 5 mg/kg followed by retreatment of any non-responders represents a potentially less costly approach in patients who fail antimony therapy. Though high cure rates are achieved with > or = 10 mg/kg total dose of ABLC, treatment using lower doses with retreatment of non-responders or relapses with higher dose can result in considerable savings.

Treatment of Indian visceral leishmaniasis with single or daily infusions of low dose liposomal amphotericin B: randomised trial.

OBJECTIVE: To test short course, low dose liposomal amphotericin B as single or daily infusion treatment in Indian visceral leishmaniasis (kala-azar). DESIGN: Randomised, open label study. SETTING: Inpatient unit for leishmaniasis in Bihar, India. PARTICIPANTS: 91 adults and children with splenic aspirate positive for infection. INTERVENTIONS: Total dose of 5 mg/kg of liposomal amphotericin B given as a single infusion (n=46) or as once daily infusions of 1 mg/kg for five days (n=45). MAIN OUTCOME MEASURES: Clinical and parasitological cure assessed 14 days after treatment and long term definitive cure (healthy, no relapse) at six months. RESULTS: All but one person in each group had an initial apparent cure. During six months of follow up, three patients in the single dose group and two in the five dose group relapsed. Complete response (definitive cure) was therefore achieved in 84 of 91 subjects (92%): 42 of 46 patients in the single dose group (91%, 95% confidence interval 79% to 98%) and 42 of 45 in the five dose group (93%, 82% to 99%). Response rates in the two groups were not significantly different. CONCLUSION: Low dose liposomal amphotericin B (5 mg/kg), given either as a five day course or as a single infusion, seems to be effective for visceral leishmaniasis and warrants further testing.

Response to interferon-gamma plus pentavalent antimony in Indian visceral leishmaniasis.

One hundred fifty-six previously untreated Indian patients with visceral leishmaniasis were treated with pentavalent antimony (Sb) alone for 30 days (group A), Sb plus interferon-gamma (IFN-gamma) for 30 days (group B), or Sb plus IFN-gamma for 15 days (group C). The purpose was to show that IFN-gamma would increase the response to 30 days of Sb treatment and that short-course (15 days) combination therapy was as effective as 30 days of Sb alone. Six months after treatment, 36% of group A, 49% of group B, and 42% of group C patients were designated as definitively cured. The success rates for long-term responses to Sb alone (36%) and Sb plus IFN-gamma (49%) were unexpectedly low, and responses in groups A, B, and C were not significantly different. These results suggest that the beneficial effects of adjunctive IFN-gamma in visceral leishmaniasis may be limited in regions where this disseminated intracellular infection shows high-level resistance to Sb.

Trial of oral miltefosine for visceral leishmaniasis.

BACKGROUND: There is no effective oral treatment for visceral leishmaniasis (kala-azar), a disseminated intracellular protozoal infection that occurs worldwide. Miltefosine, an alkyl phospholipid developed as an oral antineoplastic agent, is active against visceral infection in animal models. We tested safety, tolerance, and efficacy of miltefosine in kala-azar. METHODS: Oral doses of miltefosine were given to six groups of five Indian men for 28 days: 50 mg every second day (group 1), 100 mg every second day (group 2), 100 mg/day (group 3), 150 mg/day (group 4), 200 mg/day (group 5), and 250 mg/day (group 6). Assessment for apparent cure--taken as an afebrile state with decreased spleen size and a splenic-aspirate parasite-density score of 0--was done on days 14 and 28. Definitive cure at 8 months required a parasite-free bone-marrow aspirate and no clinical evidence of relapse. FINDINGS: 21 of 30 patients were apparently cured on day 14. Transient episodes of vomiting and diarrhoea, were common during weeks 1-2 and were seen in 22 patients. Four other patients in groups 5 and 6 had miltefosine withdrawn after 7-10 days because of vomiting. One patient in group 6 developed renal insufficiency and severe diarrhoea and died on day 21. On day 28, all 29 remaining patients were apparently cured. By 8 months, seven of ten patients in groups 1 and 2 had relapsed; however, 18 of 19 patients treated daily (groups 3-6) appeared to be cured. Among the 21 definitive cures were the four patients treated for 10 days or less and 12 for whom previous therapy with pentavalent antimony had failed. INTERPRETATION: Treatment with miltefosine at 100-150 mg/day for 4 weeks has promise as an effective oral treatment of visceral leishmaniasis including antimony-resistant infection.

Oral treatment of visceral leishmaniasis with miltefosine.

In a pilot trial, 28 days of oral treatment with 100-200 mg miltefosine (hexadecylphosphocholine) per day cured 14 of 15 patients with Indian visceral leishmaniasis (VL). To extend the testing of this regimen, 45 additional subjects with VL, of whom 17 had failed previous antimony therapy, were treated with 100 (N = 17), 150 (N = 18) or 200 (N = 10) mg/day. Enrollment at 200 mg/day was stopped after three subjects in this treatment arm developed reversible but serious (grade-3) adverse reactions. The overall clinical and parasitological responses to miltefosine were rapid, with 40 [89%; 95% confidence interval (CI) = 76%-96%] and 44 (98%; CI = 88%-100%) of the patients apparently cured on days 14 and 28, respectively. The one 'treatment failure' recorded on day 28 (and at 6 months) was a subject lost to follow-up. Those apparently cured by day 28 included six patients (one on 100 mg, two on 150 mg and three on 200 mg/day) removed from treatment on days 7-17 because of grade-3 diarrhoea (two cases), vomiting (two cases), diarrhoea and hepatotoxicity (one case) or nephrotoxicity (one case). Transient, mild-moderate vomiting and/or diarrhoea were common during weeks 1-2 and about 25% of the patients also developed primarily mild, self-limited increases in concentrations of aspartate aminotransferase and creatinine and/or blood urea nitrogen. At a 6-month follow-up, all 44 patients apparently cured at day 28 were considered complete responders (definitive cures), including the six treated for only 7-17 days. These results indicate that 100 mg miltefosine/day for 28 days is a promising oral-treatment regimen for VL cases, including those with antimony-unresponsive infections.