Gautham Ravipati

Type 5 phosphodiesterase inhibitors in the treatment of erectile dysfunction and cardiovascular disease.

Since the discovery of sildenafil in 1989 as a highly selective inhibitor of the phosphodiesterase type-5 (PDE-5) receptor, 2 additional PDE-5 inhibitors, tadalafil and vardenafil, have emerged as safe and effective treatments of erectile dysfunction (ED). Enzymes in the PDE family catalyze the hydrolysis of the intracellular signaling molecules cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which is the second messenger of nitric oxide (NO) and a principal mediator of smooth muscle relaxation and vasodilation. Sildenafil was initially introduced for clinical use as the result of extensive research on chemical agents targeting PDE-5 that might potentially be useful in the treatment of coronary heart disease. Erection is largely a hemodynamic event, which is regulated by vascular tone and blood flow balance in the penis. Endothelial dysfunction, an early component of atherosclerosis, may inhibit a vascular event such as erection and is rarely confined to the arteries supplying blood to the penis, but more likely occurs throughout the vascular bed. In addition to the effects of the NO-cGMP signaling pathway on cavernosal smooth muscle, clinical findings have suggested that vascular tone in the pulmonary, coronary, and other vascular tissues expressed by PDE-5 is also influenced by this signal transduction mechanism. This has led to the emergence of novel therapeutic indications for sildenafil over a range of cardiovascular conditions that are either well-established risk factors or comorbidities with ED. Recently, the U.S. Food and Drug Administration approved sildenafil as an orally active therapy for the treatment of primary pulmonary hypertension. The drug will be marketed under the trade name of Revatio, not Viagra, the name used for the ED indication. The approved dose for primary pulmonary hypertension is 20 mg 3 times daily.

Comparison of sensitivity, specificity, positive predictive value, and negative predictive value of stress testing versus 64-multislice coronary computed tomography angiography in predicting obstructive coronary artery disease diagnosed by coronary angiography.

Sixty-four-multislice coronary computed tomographic angiography (CTA) and coronary angiography were performed in 145 patients (mean age 67 +/- 10 years), and stress testing was performed in 47 of these patients to determine the sensitivity, specificity, positive predictive value, and negative predictive value of coronary CTA and of stress testing in diagnosing obstructive coronary artery disease (CAD) in patients with suspected CAD. In 145 patients, coronary CTA had 98% sensitivity, 74% specificity, 90% positive predictive value, and 94% negative predictive value in diagnosing obstructive CAD. In 47 patients, stress testing had 69% sensitivity, 36% specificity, 78% positive predictive value, and 27% negative predictive value for diagnosing obstructive CAD, whereas coronary CTA had 100% sensitivity, 73% specificity, 92% positive predictive value, and 100% negative predictive value for diagnosing obstructive CAD. In conclusion, coronary CTA has better sensitivity, specificity, positive predictive value, and negative predictive value than stress testing in diagnosing obstructive CAD.

Prevalence of Moderate or Severe Left Ventricular Diastolic Dysfunction in Obese Persons with Obstructive Sleep Apnea

We investigated prior to gastric bypass surgery the prevalence of left ventricular diastolic dysfunction (LVDD) by Doppler and tissue Doppler echocardiography in 14 obese women and in 6 obese men, mean age 45 years, with a mean body mass index of 49 ± 5 kg/m2 who had nocturnal polysomnography for obstructive sleep apnea (OSA). The Doppler and tissue Doppler echocardiographic data were analyzed blindly without knowledge of the clinical characteristics or whether OSA was present or absent. Of 20 patients, 8 (40%) had no OSA, 4 (20%) had mild OSA, and 8 (40%) had moderate or severe OSA. Moderate or severe LVDD was present in 4 of 8 patients (50%) with moderate or severe OSA and in none of 12 patients (0%) with no or mild OSA (p < 0.01). Obese patients with moderate or severe OSA have a higher prevalence of moderate or severe LVDD than obese patients with no or mild OSA.

Association of diet alone, insulin, sulfonylureas, metformin, and thiazolidinediones with the severity of coronary artery disease in patients with diabetes mellitus.

Coronary angiography was performed in 152 men and 163 women with diabetes mellitus, mean age 55 ± 8 years, because of chest pain. Of 67 patients with 3-vessel or 4-vessel coronary artery disease (CAD), 17 (25%) were treated with diet alone, 29 (43%) with insulin, 18 (27%) with sulfonylureas, 12 (18%) with metformin, and 6 (9%) with thiazolidinediones. Of 76 patients with 2-vessel CAD, 20 (26%) were treated with diet alone, 36 (47%) with insulin, 21 (28%) with sulfonylureas, 21 (28%) with metformin, and 11 (14%) with thiazolidinediones. Of 40 patients with 1-vessel CAD, 15 (38%) were treated with diet alone, 11 (28%) with insulin, 8 (20%) with sulfonylureas, 12 (30%) with metformin, and 4 (10%) with thiazolidinediones. Of 132 patients with 0-vessel CAD, 18 (14%) were treated with diet alone, 21 (16%) with insulin, 7 (5%) with sulfonylureas, 75 (56%) with metformin, and 35 (26%) with thiazolidinediones. Cochran-Armitage trend tests were used to examine whether the use of treatment significantly increases or decreases as the number of arteries with CAD increases (P = 0.036 for diet alone; P < 0.0001 for insulin, for sulfonylureas, and for metformin; P = 0.002 for thiazolidinediones).

Incidence of new stroke or new myocardial infarction or death at 39-month follow-up in patients with diabetes mellitus, hypertension or both with and without microalbuminuria

We investigated in 306 patients, mean age 57 ± 10 years, with diabetes mellitus (202 patients) or hypertension (179 patients) whether microalbuminuria was a significant independent risk factor for the development of new stroke or new myocardial infarction (MI) or death. At 39-month follow-up, new stroke or new MI or death developed in 44 of 111 patients (40%) with microalbuminuria and in 38 of 195 patients (19%) without microalbuminuria (p = 0.0001). Stepwise Cox regression analysis showed that significant independent predictors of the time to development of new stroke or new MI or death were (1) diabetes (risk ratio = 1.76), (2) left ventricular (LV) mass index (risk ratio = 1.020 for each 1 g/m2 increase), (3) prior stroke (risk ratio = 5.39), and (4) prior MI (risk ratio = 3.29). Microalbuminuria was not a significant independent predictor of new stroke or new MI or death, but LV mass index, diabetes mellitus, prior stroke, and prior MI were significant independent predictors.

Incidence of new stroke or new myocardial infarction or death at 39-month follow up in patients with diabetes mellitus, hypertension, or both treated with and without angiotensin-converting enzyme inhibitors or angiotensin receptor blockers

We investigated in 306 patients, mean age 57 ± 10 years, with diabetes mellitus (202 patients) or hypertension (179 patients), whether treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ARBs) reduced the incidence of new stroke or new myocardial infarction (MI) or death. At 39-month follow up, new stroke or new MI or death developed in 49 of 228 patients (21%) treated with ACE inhibitors or ARBs and in 33 of 78 patients (42%) treated without angiotensin-converting enzyme inhibitors or ARBs (P = 0.0001). Stepwise Cox regression analysis showed that significant independent predictors of the time to development of new stroke or new MI or death were 1) use of angiotensin-converting enzyme inhibitors or ARBs (risk ratio, 0.21), 2) diabetes (risk ratio, 4.01), 3) left ventricular hypertrophy (risk ratio, 6.71), 4) prior stroke (risk ratio, 4.00), and 5) prior MI (risk ratio, 3.69).

Pseudoaneurysm with thrombus and left ventricular inflow obstruction after left circumflex stenting.

A 61-year-old woman had stenting of the left circumflex coronary artery. She had a repeat coronary angiogram the day after stenting because of hypotension and orthopnea. The left circumflex stent was patent. A transesophageal echocardiogram showed a 2.5 cm x 3.0-cm mass in the atrioventricular groove compressing the left atrium. A pseudoaneurysm with thrombus and left ventricular inflow obstruction was diagnosed. The patient was observed for 48 hours to allow the pseudoaneurysm to seal and coagulate. She then had surgical evacuation of the thrombus, which had caused her hypotension and orthopnea by compression of the left atrium.

COMPARISON OF LEFT VENTRICULAR EJECTION FRACTION BY SINGLE PHOTON COMPUTED TOMOGRAPHIC MYOCARDIAL PERFUSION IMAGING VERSUS CORONARY COMPUTED TOMOGRAPHY ANGIOGRAPHY

Introduction: Measurement of left ventricular (LV) ejection fraction by coronary computed tomography angiography (CTA) vs. single photon computed tomographic myocardial perfusion imaging (MPI) needs to be investigated. Material and methods: Myocardial perfusion imaging and CTA were performed in 292 patients because of chest pain or dyspnea. The patients included 178 men and 114 women, mean age 66 ±11 years. Results: The mean LV ejection fraction was 61 ±12% for the MPI tests and 65 ±11% for CTA (p <0.001). The LV ejection fraction was ≥ 50% in 250 of 292 patients (86%) with MPI testing and in 266 of 292 patients (91%) with CTA (p < 0.05). The LV ejection fraction was 36-49% in 31 of 292 patients (11%) with MPI testing and in 22 of 292 patients (8%) with CTA (p not significant). The LV ejection fraction was ≤ 35% in 11 of 292 patients (4%) with MPI testing and in 4 of 292 patients (1%) with CTA (p not significant). Pearson correlation coefficient was R = 0.67, p < 0.001. Conclusions: The resting LV ejection fraction is significantly higher in patients measured by CTA than in patients measured by MPI testing when both tests are performed in the same patients.