Manikantam Gaddam

All Publications

• Septal annular dilation in chronic ovine functional tricuspid regurgitation. The Journal of thoracic and cardiovascular surgery Iwasieczko, A., Jazwiec, T., Gaddam, M., Gaweda, B., Piekarska, M., Solarewicz, M., Rausch, M. K., Timek, T. A. 2023; 166 (5): e393-e403

  Abstract

  INTRODUCTION: Annular reduction with prosthetic rings represents the current surgical treatment of functional tricuspid regurgitation (FTR). However, alterations of annular geometry and dynamics associated with FTR are not well characterized.METHODS: FTR was induced in 29 adult sheep with either 8 weeks of pulmonary artery banding (PAB, n=15) or 3weeks of tachycardia-induced cardiomyopathy (TIC, n=14). Eight healthy sheep served as controls (CTL). At the terminal procedure, all animals underwent sternotomy, epicardial echocardiography, and implantation of sonomicrometry crystals on the tricuspid annulus (TA) and right ventricular free wall while on cardiopulmonary bypass. Simultaneous hemodynamic, sonomicrometry, and echocardiographic data were acquired after weaning from cardiopulmonary bypass and stabilization. Annular geometry and dynamics were calculated from 3-dimensional crystal coordinates.RESULTS: Mean FTR grade (0-4) was 3.2± 1.2 and 3.2± 0.5 for PAB and TIC, respectively, with both models of FTR associated with similar degree of right ventricular dysfunction (right ventricular fractional area contraction 38± 7% and 37± 9% for PAB and TIC, respectively). Left ventricular ejection fraction was significantly reduced in TIC versus baseline (33± 9%, vs 58± 4%, P=.0001). TA area was 651± 109 mm2, 881± 242 mm2, and 995± 232mm2 for CTL, FTR, and TIC, respectively (P=.006) with TA area contraction of 16.6± 4.2%, 11.5± 8.0%, and 6.0± 4.0%, respectively (P=.003). Septal annulus increased from 33.8± 3.1 mm to 39.7± 6.4 mm and 43.1± 3.2mm for CTL, PAB, and TIC, respectively (P<.0001).CONCLUSIONS: Ovine FTR was associated with annular dilation and reduced annular area contraction. Significant dilation of septal annulus was observed in both models of FTR. As tricuspid rings do not completely stabilize the septal annulus, continued remodeling may contribute to recurrent FTR after repair.

  View details for DOI 10.1016/j.jtcvs.2023.04.003

  View details for PubMedID 37061178

• Effect of Papillary Muscle Approximation on Acute Ovine Functional Tricuspid Regurgitation. Interdisciplinary cardiovascular and thoracic surgery Gaweda, B., Jazwiec, T., Gaddam, M., Bush, J. D., MacDougall, B., Widenka, K., Timek, T. A. 2023

  Abstract

  OBJECTIVES: Ring annuloplasty represents the standard surgical treatment, but offers suboptimal results in patients with severe functional tricuspid regurgitation. Addition of papillary muscles approximation may improve clinical outcomes.METHODS: Eight healthy adult male sheep (56±4kg) underwent cardiopulmonary bypass and implantation of sonomicrometry crystals on the tricuspid annulus, papillary muscle tips and right ventricular free wall. Papillary approximation sutures were anchored between anterior-posterior and anterior-septal papillary muscles and their loose ends externalized through right ventricular free wall to epicardial tourniquets. After weaning from cardiopulmonary bypass, acute right heart failure and tricuspid regurgitation were induced, and subsequent sequential anterior-posterior and anterior-septal papillary muscle approximations were performed. Echocardiographic, haemodynamic and sonomicrometry data were collected.RESULTS: Tricuspid regurgitation at baseline in eight sheep was none or trace in 3 and mild in 5, and after induction of acute right heart failure increased significantly to moderate in 5, moderately severe in 1 and severe in 2 (p=0.011). Right ventricular pressure increased from 31 [28; 43] to 51 [47; 55] mmHg (p=0.012). Anterior-posterior papillary muscle approximation decreased regurgitation grade to none or trace in 1, mild in 4, and moderate in 3 (p=0.016), and reduced papillary muscle area from 208 [160; 241] to 108 [48; 181] mm2, p=0.008), and anterior-posterior papillary muscle distance from 18 [16; 20] to 10[7; 13] mm, p=0.037). Anterior-septal approximation also significantly reduced papillary muscle area but had no effect on regurgitation grade.CONCLUSIONS: Anterior-posterior but not anterior-septal papillary muscle approximation alleviated acute ovine tricuspid regurgitation. Selective papillary muscle approximation may offer better control of tricuspid regurgitation.

  View details for DOI 10.1093/icvts/ivad098

  View details for PubMedID 37348860

• Papillary Muscle Approximation in Chronic Ovine Functional Tricuspid Regurgitation. The Journal of thoracic and cardiovascular surgery Gaweda, B., Gaddam, M., Jaźwiec, T., Bush, J. D., MacDougall, B., Widenka, K., Timek, T. A. 2023

  Abstract

  Isolated tricuspid ring annuloplasty remains the surgical standard for functional tricuspid regurgitation repair but offers suboptimal results when right ventricular dilation and remodeling along with papillary muscle displacement is present. Addressing subvalvular remodeling with papillary muscle approximation may improve clinical outcomes.Functional tricuspid regurgitation and biventricular dysfunction were induced in eight healthy sheep by rapid ventricular pacing (200-240 b/min) for 27±6 days. Subsequently, animals underwent cardiopulmonary bypass for implantation of sonomicrometry crystals on the tricuspid annulus, right ventricle, and papillary muscle tips. Papillary approximation sutures were anchored between anterior-posterior and anterior-septal papillary muscles and externalized through right ventricular free wall to epicardial tourniquets. After weaning from cardiopulmonary bypass, sequential papillary muscle approximations were performed. Simultaneous hemodynamic, sonomicrometry, and echocardiographic data were collected at baseline and after each papillary muscle approximation.With rapid pacing, right ventricular fractional area change decreased from 59±6 to 38 ±8% (p<0.001) while tricuspid annulus diameter increased from 2.4±0.3 to 3.3±0.6 cm (p=0.003). Tricuspid regurgitation (0-4+) increased from +0±0 to +3.3±0.7 (p<0.001). Both anterior-posterior and anterior-septal papillary muscle approximation significantly reduced functional tricuspid regurgitation from +3.3±0.7 to +2±0.5 and +1.9±0.6, respectively (p<0.001). Reduction of tricuspid insufficiency with both subvalvular interventions was associated with decreased distance of the anterior papillary muscle to the annular centroid.Papillary muscle approximations were effective in reducing severe ovine functional tricuspid regurgitation associated with right ventricular dilation and papillary muscle displacement. Further studies are needed to evaluate efficacy of this adjunct to ring annuloplasty in repair of severe FTR.

  View details for DOI 10.1016/j.jtcvs.2023.05.039

  View details for PubMedID 37330209

• Valvular complex and tissue remodelling in ovine functional tricuspid regurgitation. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Iwasieczko, A., Gaddam, M., Gaweda, B., Goodyke, A., Mathur, M., Lin, C., Zagorski, J., Solarewicz, M., Cohle, S., Rausch, M., Timek, T. A. 2023; 63 (5)

  Abstract

  OBJECTIVES: Pathophysiology of function tricuspid regurgitation (FTR) is incompletely understood. We set out to comprehensively evaluate geometric and tissue remodelling of the tricuspid valve complex in ovine FTR.METHODS: Twenty adult sheep underwent left thoracotomy and pulmonary artery banding (PAB) to induce right heart pressure overload and FTR. After 8 weeks, 17 surviving animals and 10 healthy controls (CTL) underwent sternotomy, echocardiography and implantation of sonomicrometry crystals on right ventricle and tricuspid valvular apparatus. Haemodynamic and sonomicrometry data were acquired in all animals after weaning from cardiopulmonary bypass. Leaflet tissue was harvested for pentachrome histologic analysis and biomechanical testing.RESULTS: Animal weight was 62 ± 5 and 63 ± 3 kg for CTL and PAB, respectively (P = 0.6). At terminal procedure, systolic pulmonary artery pressure was 22 ± 3 and 40 ± 7 mmHg for CTL and PAB, respectively (P = 0.0001). The mean TR grade (+0-4) was 0.8 ± 0.4 and 3.2 ± 1.2 (P = 0.0001) for control and banded animals, respectively. Right ventricle volume (126 ± 13 vs 172 ± 34 ml, P = 0.0019), tricuspid annular area (651 ± 109 vs 865 ± 247 mm2, P = 0.037) and area between papillary muscle tips (162 ± 51 vs 302 ± 75 mm2, P = 0.001) increased substantially while systolic excursion of anterior leaflet decreased significantly (23.8 ± 6.1° vs 7.4 ± 4.5°, P = 0.001) with banding. Total leaflet surface area increased from 806 ± 94 to 953 ± 148 mm2 (P = 0.009), and leaflets became thicker and stiffer.CONCLUSIONS: Detailed analysis of the tricuspid valve complex revealed significant ventricular, annular, subvalvular and leaflet remodelling to be associated with ovine functional tricuspid regurgitation. Durable surgical repair of severe FTR may require a multi-level approach to the valvular apparatus.

  View details for DOI 10.1093/ejcts/ezad115

  View details for PubMedID 36951551

• Chronic Ovine Model of Right Ventricular Failure and Functional Tricuspid Regurgitation. Journal of visualized experiments : JoVE Gaweda, B., Iwasieczko, A., Gaddam, M., Bush, J. D., MacDougal, B., Timek, T. A. 2023

  Abstract

  The pathophysiology of severe functional tricuspid regurgitation (FTR) associated with right ventricular dysfunction is poorly understood, leading to suboptimal clinical results. We set out to establish a chronic ovine model of FTR and right heart failure to investigate the mechanisms of FTR. Twenty adult male sheep (6-12 months old, 62 ± 7 kg) underwent a left thoracotomy and baseline echocardiography. A pulmonary artery band (PAB) was placed and cinched around the main pulmonary artery (PA) to at least double the systolic pulmonary artery pressure (SPAP), inducing right ventricular (RV) pressure overload and signs of RV dilatation. PAB acutely increased the SPAP from 21 ± 2 mmHg to 62 ± 2 mmHg. The animals were followed for 8 weeks, symptoms of heart failure were treated with diuretics, and surveillance echocardiography was used to assess for pleural and abdominal fluid collection. Three animals died during the follow-up period due to stroke, hemorrhage, and acute heart failure. After 2 months, a median sternotomy and epicardial echocardiography were performed. Of the surviving 17 animals, 3 developed mild tricuspid regurgitation, 3 developed moderate tricuspid regurgitation, and 11 developed severe tricuspid regurgitation. Eight weeks of pulmonary artery banding resulted in a stable chronic ovine model of right ventricular dysfunction and significant FTR. This large animal platform can be used to further investigate the structural and molecular basis of RV failure and functional tricuspid regurgitation.

  View details for DOI 10.3791/64529

  View details for PubMedID 37010284

• The Presence of a Substrate Strengthens The Jet Generated by Upside-Down Jellyfish FRONTIERS IN MARINE SCIENCE Battista, N., Gaddam, M. G., Hamlet, C. L., Hoover, A. P., Miller, L. A., Santhanakrishnan, A. 2022; 9

  View details for DOI 10.3389/fmars.2022.847061

  View details for Web of Science ID 000801773800001