Browsing by Author "Vemulapalli, Sreekanth"

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    Apparent treatment-resistant hypertension and chronic kidney disease: another cardiovascular-renal syndrome?
    (Adv Chronic Kidney Dis, 2014-11) Vemulapalli, Sreekanth; Tyson, Crystal C; Svetkey, Laura P
    To identify patients at increased risk of cardiovascular (CV) outcomes, apparent treatment-resistant hypertension (aTRH) is defined as having a blood pressure above goal despite the use of 3 or more antihypertensive therapies of different classes at maximally tolerated doses, ideally including a diuretic. Recent epidemiologic studies in selected populations estimated the prevalence of aTRH as 10% to 15% among patients with hypertension and that aTRH is associated with elevated risk of CV and renal outcomes. Additionally, aTRH and CKD are associated. Although the pathogenesis of aTRH is multifactorial, the kidney is believed to play a significant role. Increased volume expansion, aldosterone concentration, mineralocorticoid receptor activity, arterial stiffness, and sympathetic nervous system activity are central to the pathogenesis of aTRH and are targets of therapies. Although diuretics form the basis of therapy in aTRH, pathophysiologic and clinical data suggest an important role for aldosterone antagonism. Interventional techniques, such as renal denervation and carotid baroreceptor activation, modulate the sympathetic nervous system and are currently in phase III trials for the treatment of aTRH. These technologies are as yet unproven and have not been investigated in relationship to CV outcomes or in patients with CKD.
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    Diagnostic Performance of Coronary Angiography Derived Computational Fractional Flow Reserve.
    (Journal of the American Heart Association, 2024-06) Vardhan, Madhurima; Tanade, Cyrus; Chen, S James; Mahmood, Owais; Chakravartti, Jaidip; Jones, W Schuyler; Kahn, Andrew M; Vemulapalli, Sreekanth; Patel, Manesh; Leopold, Jane A; Randles, Amanda

    Background

    Computational fluid dynamics can compute fractional flow reserve (FFR) accurately. However, existing models are limited by either the intravascular hemodynamic phenomarkers that can be captured or the fidelity of geometries that can be modeled.

    Methods and results

    This study aimed to validate a new coronary angiography-based FFR framework, FFRHARVEY, and examine intravascular hemodynamics to identify new biomarkers that could augment FFR in discerning unrevascularized patients requiring intervention. A 2-center cohort was used to examine diagnostic performance of FFRHARVEY compared with reference wire-based FFR (FFRINVASIVE). Additional biomarkers, longitudinal vorticity, velocity, and wall shear stress, were evaluated for their ability to augment FFR and indicate major adverse cardiac events. A total of 160 patients with 166 lesions were investigated. FFRHARVEY was compared with FFRINVASIVE by investigators blinded to the invasive FFR results with a per-stenosis area under the curve of 0.91, positive predictive value of 90.2%, negative predictive value of 89.6%, sensitivity of 79.3%, and specificity of 95.4%. The percentage ofdiscrepancy for continuous values of FFR was 6.63%. We identified a hemodynamic phenomarker, longitudinal vorticity, as a metric indicative of major adverse cardiac events in unrevascularized gray-zone cases.

    Conclusions

    FFRHARVEY had high performance (area under the curve: 0.91, positive predictive value: 90.2%, negative predictive value: 89.6%) compared with FFRINVASIVE. The proposed framework provides a robust and accurate way to compute a complete set of intravascular phenomarkers, in which longitudinal vorticity was specifically shown to differentiate vessels predisposed to major adverse cardiac events.
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    Left Atrial Appendage Occlusion Versus Oral Anticoagulation in Atrial Fibrillation : A Decision Analysis.
    (Annals of internal medicine, 2022-08) Chew, Derek S; Zhou, Ke; Pokorney, Sean D; Matchar, David B; Vemulapalli, Sreekanth; Allen, Larry A; Jackson, Kevin P; Samad, Zainab; Patel, Manesh R; Freeman, James V; Piccini, Jonathan P

    Background

    Left atrial appendage occlusion (LAAO) is a potential alternative to oral anticoagulants in selected patients with atrial fibrillation (AF). Compared with anticoagulants, LAAO decreases major bleeding risk, but there is uncertainty regarding the risk for ischemic stroke compared with anticoagulation.

    Objective

    To determine the optimal strategy for stroke prevention conditional on a patient's individual risks for ischemic stroke and bleeding.

    Design

    Decision analysis with a Markov model.

    Data sources

    Evidence from the published literature informed model inputs.

    Target population

    Women and men with nonvalvular AF and without prior stroke.

    Time horizon

    Lifetime.

    Perspective

    Clinical.

    Intervention

    LAAO versus warfarin or direct oral anticoagulants (DOACs).

    Outcome measures

    The primary end point was clinical benefit measured in quality-adjusted life-years.

    Results of base-case analysis

    The baseline risks for stroke and bleeding determined whether LAAO was preferred over anticoagulants in patients with AF. The combined risks favored LAAO for higher bleeding risk, but that benefit became less certain at higher stroke risks. For example, at a HAS-BLED score of 5, LAAO was favored in more than 80% of model simulations for CHA2DS2-VASc scores between 2 and 5. The probability of LAAO benefit in QALYs (>80%) at lower bleeding risks (HAS-BLED score of 0 to 1) was limited to patients with lower stroke risks (CHA2DS2-VASc score of 2). Because DOACs carry lower bleeding risks than warfarin, the net benefit of LAAO is less certain than that of DOACs.

    Results of sensitivity analysis

    Results were consistent using the ORBIT bleeding score instead of the HAS-BLED score, as well as alternative sources for LAAO clinical effectiveness data.

    Limitation

    Clinical effectiveness data were drawn primarily from studies on the Watchman device.

    Conclusion

    Although LAAO could be an alternative to anticoagulants for stroke prevention in patients with AF and high bleeding risk, the overall benefit from LAAO depends on the combination of stroke and bleeding risks in individual patients. These results suggest the need for a sufficiently low stroke risk for LAAO to be beneficial. The authors believe that these results could improve shared decision making when selecting patients for LAAO.

    Primary funding source

    None.
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    Major bleeding in patients with peripheral artery disease: Insights from the EUCLID trial.
    (American heart journal, 2019-11-18) Ward, Rachael; Huang, Zhen; Rockhold, Frank W; Baumgartner, Iris; Berger, Jeffrey S; Blomster, Juuso I; Fowkes, F Gerry R; Katona, Brian G; Mahaffey, Kenneth W; Norgren, Lars; Vemulapalli, Sreekanth; Povsic, Thomas J; Mehta, Rajendra; Hiatt, William R; Patel, Manesh R; Jones, W Schuyler
    BACKGROUND:Rates and predictors of major bleeding in patients with peripheral artery disease (PAD) treated with antiplatelets have not been well studied. This post hoc analysis of EUCLID aimed to determine the incidence of major/minor bleeding, predictors of major bleeding, and risk of major adverse cardiovascular events (MACE) following major bleeding events. METHODS:EUCLID, a multicenter randomized controlled trial of 13,885 patients with symptomatic PAD, compared ticagrelor with clopidogrel for the prevention of MACE. The primary safety end point was Thrombolysis in Myocardial Infarction (TIMI) major bleeding. Baseline characteristics were used to develop a multivariable model to determine factors associated with TIMI major bleeding. The occurrence and timing of MACE relative to a first major bleeding event were determined. RESULTS:TIMI major bleeding occurred in 2.3% of participants overall (0.94 event/100 patient-years). There was no significant difference in major bleeding rates by treatment assignment. Factors associated with TIMI major bleeding included older age, geographic region, Rutherford class, and β-blocker use. Patients with TIMI major bleeding postrandomization had an increased risk of MACE (hazard ratio [HR] 4.46; 95% CI 3.40-5.84; P < .0001) compared with those without major bleeding; the association was strongest within 30 days after a bleeding event. CONCLUSIONS:In patients with symptomatic PAD, 0.94 major bleeding event/100 patient-years was observed and associated with older age, residing in North America, disease severity, and β-blocker use. Patients who had a major bleeding event were significantly more likely to experience MACE, especially within the first 30 days, when compared with patients who did not have major bleeding.