Cardiology

Posted July 15th 2021

Ultrasound-Targeted Microbubble Destruction Mediates Gene Transfection for Beta-Cell Regeneration and Glucose Regulation.

Paul A. Grayburn M.D.

Paul A. Grayburn M.D.

Zhang, C., Chen, S., Li, Q., Wu, J., Qiu, F., Chen, Z., Sun, Y., Luo, J., Bastarrachea, R.A., Grayburn, P.A., DeFronzo, R.A., Liu, Y., Qian, K. and Huang, P. (2021). “Ultrasound-Targeted Microbubble Destruction Mediates Gene Transfection for Beta-Cell Regeneration and Glucose Regulation.” Small Jun 29;e2008177. [Epub ahead of print]. e2008177.

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Ultrasound-targeted microbubble destruction (UTMD) mediates gene transfection with high biosafety and thus has been promising toward treatment of type 1 diabetes. However, the potential application of UTMD in type 2 diabetes (T2D) is still limited, due to the lack of systematic design and dynamic monitoring. Herein, an efficient gene delivery system is constructed by plasmid deoxyribonucleic acid (DNA) encoding glucagon-like peptide 1 (GLP-1) in ultrasound-induced microbubbles, toward treatment of T2D in macaque. The as designed UTMD afforded enhancement of cell membrane penetration and GLP-1 expression in macaque, which is characterized by ultrasound-guided biopsy to monitor the dynamic process of islet cells for 6 months. Also, improvement of pancreatic beta cell regeneration, and regulation of plasma glucose in macaque with T2D is achieved. The approach would serve as promising alternatives for the treatment of T2D.


Posted July 15th 2021

A retrospective study on the therapeutic effects of sodium bicarbonate for adult in-hospital cardiac arrest.

Eric Chou, M.D.

Eric Chou, M.D.

Wang, C.H., Wu, C.Y., Wu, M.C., Chang, W.T., Huang, C.H., Tsai, M.S., Lu, T.C., Chou, E., Hsieh, Y.L. and Chen, W.J. (2021). “A retrospective study on the therapeutic effects of sodium bicarbonate for adult in-hospital cardiac arrest.” Sci Rep 11(1): 12380.

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To investigate whether the effects of sodium bicarbonate (SB) during cardiopulmonary resuscitation (CPR) would be influenced by blood pH and administration timing. Adult patients experiencing in-hospital cardiac arrest (IHCA) from 2006 to 2015 were retrospectively screened. Early intra-arrest blood gas data were obtained within 10 min of CPR. Multivariable logistic regression analysis and generalised additive models were used for effect estimation and data exploration, respectively. A total of 1060 patients were included. Only 59 patients demonstrated favourable neurological status at hospital discharge. Blood pH ≤ 7.18 was inversely associated with favourable neurological outcome (odds ratio [OR], 0.24; 95% confidence interval [CI], 0.11-0.52; p value < 0.001) while SB use was not. In the interaction analysis for favourable neurological outcome, significant interactions were noted between SB use and time to SB (SB use × time to SB ≥ 20 min; OR 6.16; 95% CI 1.42-26.75; p value = 0.02). In the interaction analysis for survival to hospital discharge, significant interactions were noted between SB use and blood pH (Non-SB use × blood pH > 7.18; OR 1.56; 95% CI 1.01-2.41; p value = 0.05). SB should not be empirically administered for patients with IHCA since its effects may be influenced by blood pH and administration timing.


Posted July 15th 2021

Impact of Predilation During Transcatheter Aortic Valve Replacement: Insights From the PARTNER 3 Trial.

Michael J. Mack M.D.

Michael J. Mack M.D.

Ternacle, J., Al-Azizi, K., Szerlip, M., Potluri, S., Hamandi, M., Blanke, P., Leipsic, J., Dahou, A., Salaun, E., Vincent, F., Rogers, E., Alu, M.C., Lu, M., Yu, X., Thourani, V.H., Hahn, R.T., Leon, M.B., Pibarot, P. and Mack, M.J. (2021). “Impact of Predilation During Transcatheter Aortic Valve Replacement: Insights From the PARTNER 3 Trial.” Circ Cardiovasc Interv Jun 18;CIRCINTERVENTIONS120010336. [Epub ahead of print]. Circinterventions120010336.

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BACKGROUND: The use of predilation during transcatheter aortic valve replacement (TAVR) is variable, and its association with outcomes remains unknown. We evaluated the impact of predilation versus no predilation (direct TAVR) in the low-risk population enrolled in the PARTNER 3 trial (Placement of Aortic Transcatheter Valves). METHODS: In the PARTNER 3 trial, 495 patients with severe symptomatic aortic stenosis underwent TAVR with the SAPIEN 3 valve. The use of predilation was left to operator discretion. The primary end point was a composite of all-cause death, stroke, or rehospitalization. Secondary end points included valve hemodynamic performance and the need for postdilation. Propensity score matching was performed. RESULTS: Predilation and direct TAVR were performed in 286 (57.8%) and 209 (42.2%) patients, respectively. Before matching, the primary end point occurrence at 30 days (3.8% versus 4.8%, P=0.604) and 1 year (8.7% versus 8.1%, P=0.831) was similar in the predilation versus direct TAVR groups. Similar results were observed after matching (202 patients in each groups). Incidence of ≥ mild paravalvular regurgitation was similar in both groups. Incidence of severe prosthesis-patient mismatch was low but higher in the predilation group versus the direct TAVR group (8.2% versus 2.6%, P=0.023). Compared with direct TAVR, the use of predilation was associated with longer procedure duration (63.2 versus 51.4 minutes, P=0.001), while the rate of postdilation did not differ between the 2 groups (24.8% versus 18.8%, P=0.150). CONCLUSIONS: Predilation and direct TAVR are safe in patients with low surgical risk and favorable aortic valve anatomy. Direct TAVR decreased the procedure duration and did not predispose to more postdilation.


Posted July 15th 2021

Off-pump myocardial revascularization with Impella 5.5-assisted for cardiogenic shock.

Giuseppe Tavilla M.D. Ph.D.

Giuseppe Tavilla M.D. Ph.D.

Tavilla, G., Beckles, D.L., Morris, P. and Reddy, R.C. (2021). “Off-pump myocardial revascularization with Impella 5.5-assisted for cardiogenic shock.” J Card Surg Jun 30. [Epub ahead of print].

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We report a case of Impella 5.5-assisted off-pump coronary artery bypass grafting for acute myocardial infarction with cardiogenic shock. The Impella 5.5 was placed in the left ventricle during the emergent procedure, and an off-pump coronary artery bypass grafting was successfully performed with exposure of all three walls of the heart. Our findings demonstrated the feasibility of off-pump coronary revascularization in three-vessel disease in a patient assisted with an Impella 5.5 percutaneous left ventricular assist device without displacement of the device during the entire perioperative period.


Posted July 15th 2021

Influence of study discontinuation during the run-in period on the estimated efficacy of sacubitril/valsartan in the PARAGON-HF trial.

Milton Packer M.D.

Milton Packer M.D.

Suzuki, K., Claggett, B., Minamisawa, M., Packer, M., Zile, M.R., Pfeffer, M.A., Chiang, L.M., Lefkowitz, M., McMurray, J.J.V., Solomon, S.D. and Desai, A.S. (2021). “Influence of study discontinuation during the run-in period on the estimated efficacy of sacubitril/valsartan in the PARAGON-HF trial.” Eur J Heart Fail Jun 11. [Epub ahead of print].

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AIMS: The 4822 patients randomized in the PARAGON-HF trial were a subset of 5746 initially eligible patients who entered sequential run-in periods. We identified patient factors associated with study discontinuation during the run-in period and estimated the implications of these discontinuations for the overall study result. METHODS AND RESULTS: We utilized multivariable logistic regression models to identify patient factors associated with study discontinuation during the run-in period. The efficacy of sacubitril/valsartan in a broader cohort approximating the full run-in population was estimated by weighting randomized patients according to the inverse probability of run-in completion. A total of 924 (16.1%) subjects failed to complete the run-in period. In multivariable models, non-completion was associated with region other than Central Europe, lower systolic blood pressure, lower serum sodium, lower haemoglobin, lower estimated glomerular filtration rate, higher N-terminal pro-B-type natriuretic peptide, higher New York Heart Association functional class, prior heart failure (HF) hospitalization, and lack of prior use of renin-angiotensin system inhibitors or beta-blocker. In repeat analysis of the effect of randomized treatment in PARAGON-HF giving greater weight to participants resembling those who failed to complete the run-in period, the incidence of HF hospitalizations and cardiovascular death was higher, and sacubitril/valsartan treatment reduced the composite of total HF hospitalizations and cardiovascular death compared with valsartan (rate ratio 0.86; 95% confidence interval 0.74-1.00). CONCLUSION: Patients with more advanced HF were at higher risk for non-completion of the run-in period in PARAGON-HF. Re-analysis of study outcomes accounting for the effect of run-in non-completion did not alter the estimated treatment effects of sacubitril/valsartan vs. valsartan.