Ischemia in special population by Dr ameet kumar from NICvD karachi..pptx

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1. Ischemia in Special Population CK D , STROKE, PAD, VHD By Dr. Ameet Kumar Resident Adult Cardiology

2. CKD Each kidney weighs 130-170gm Receives blood flow of 400ml/min/100gm Approx. 20-25% of total cardiac output Kidneys consume 8% of O2 of body Interaction between heart and kidneys occurs at RAAS, Sympathetic Nervous System, Vasopressin, Endothelium, Natriuretic Peptide. Definition : An eGFR of less than 60ml/min/1.73cm2 Cr is a crude indicator of renal function, eGFR / Cr Clearance better.

3. Cystatin C , a protein found in cells and produced constantly by the body. Its filtered by healthy kidneys, in CKD its level rises in body. Normal : 0.47-1.03 mg/L

4. Contrast Induced Acute Kidney Injury (CI-AKI) >0.3mg/dl rise in Cr from baseline within 48hrs or >50% elevation in Cr from baseline. The National Cardiovascular Data Registry Cath -PCI (n=985737) reported 7% cases of CI-AKI, and 0.3% cases of AKI requiring dialysis. Transient rise in Cr are associated with longer hospital & ICU stays, MI, Stroke, HF, re-hospitalization & death. Prevention incudes 1- Intravascular volume expansion 2- Choice & quality of contrast material 3- Post-procedural monitoring. Numerous trials compared isotonic bicarb solution to i /v saline, but shows no difference in the rate of renal outcome. The lower the eGFR the less contrast material may cause AKI. Desireable contrast limit <30ml for diagnostic & <100ml for interventional procedure. For stage procedure more than 10 days gap between 1 st & 2 nd contrast exposure is desireable if CI-AKI has occurred.

5. Stroke A TIA or Stroke is a signal of underlying cerebrovascular & cardiovascular disease, and puts the patient at a higher risk of other CVD events (MI, vascular deaths etc). The Clopidogrel vs Asprin in Patients at Risk of Ischemic Events (CAPRIE) trail, Clopidogrel monotherapy given to patients with a history of MI, Stroke or symptomatic PAD reduces the combined risk of MI, Stroke or vascular deaths by 8.7% compared with asprin . Combination of clopidogrel and asprin does reduce the rate of MI, Stroke or cardiovascular deaths more than asprin alone in patients with CVD. The Women’s Health Study randomized healthy women to 100mg every other day ASA vs placebo for 10 years of treatment, although there was no significant effect on combined endpoint of MI, CVD deaths, there was a significant 24% reduction in ischemic stroke. Serious G.I bleeding was increased significantly.

6. Concomitant Acute Coronary Syndrome and Acute Ischemic Stroke: A Particular Association and a Therapeutic Dilemma Cardiocerebral infarction (CCI), defined as the concomitant occurrence of acute myocardial infarction (AMI) and acute ischaemic stroke (AIS), has been rarely reported in the literature, due to the rarity of this co-occurrence. The case of two young women admitted to cardiology department with acute coronary syndrome concomitant with stroke at different times and whose management differed according to their ischemic and hemorrhagic risk. It was assumed that there is a possible relationship between the two conditions rather than a mere coincidence. In a prospective study published in 1984, Rokey et al. reported the prevalence of CAD as 58% among patients presenting with transient ischemic attack and AIS compared with 7% in other age matched patients in the same institution. Chin et al. reported the incidence of CCI as 12.7% in geriatric patients who were screened for AMI within 72 hours of admission for acute stroke. Findings from the Global Registry of Acute Coronary Event (GRACE) trial reported an incidence of in-hospital stroke as 0.9% in a cohort of patients presenting with acute coronary syndrome, and the incidence was much higher in patients with STEMI than the non-STEMI. The most recent data in 2017 from Yeo et al. showed that 6% of patients with acute stroke had ST segment elevation.

7. Conclusion: The appropriate management of CCI represents a great challenge for practitioners. There are currently no clinical trials or consensus guidelines for the concomitant management of AMI and AIS. It is necessary to identify a federative dose of intravenous thrombolytic, the optimal duration of administration, the role of antiplatelet agents and combined coronary and cerebral endovascular interventions

8. Peripheral Arterial Disease - PAD The benefits of antithrombotic therapy for Major Adverse Cardiovascular Events (MACE) reduction & particularly more intensive strategies may be greatest in those with PAD & concomittent symptomatic CAD vs PAD without symptomatic CAD. The Antithrombotic Trails (ATT) collaboration meta-analysis of >9000 patients with symptomatic PAD showed a 23% reduction in vascular deaths, MI, Stroke with antiplatelet monotherapy . There were no reported benefits for Major Adverse Limb Events (MALE) MALE -- Amputation of revascularised limb, reintervention of the revascularised segment, loss of patency.

9. The Clopidogrel vs Asprin in Patients at Risk of Ischemic Events (CAPRIE) Trial compared clopidogrel with asprin in reducing ischemic events in patients with recent MI, recurrent ischemic stroke or PAD. Overall clopidogrel reduced vascular deaths, MI, or Stroke by 8.7% vs Asprin in PAD subgroup. Clopidogrel treatment appeared to be associated with a greater 23.8% relative risk reduction. There were more amputations with clopidogrel than asprin (52 vs 47).

10. The Platelet InhibItion and Patient Outcomes (PLATO) trial showed superiority for Ticagrelor over Clopidogrel for MACE in patients with ACS including those with PAD.

11. The Examining Use of Ticagrelor In Peripheral Artery Disease (EUCLID) trial showed no difference between Ticagrelor vs Clopidogrel for MACE in patients with ACS including PAD.

12. The Clopidogrel for High Atherothrombotic Risk and Ischemia Stabilization, Management, and Avoidance (CHARISMA) trial evaluated the addition of clopidogrel to asprin vs asprin alone in patients with established CAD, cerebrovascular disease or PAD. There was no reported benefit for MALE. There was a reduction in hospitalization that may have been attributed to limb ischemia events.

13. The Prevention with Ticagrelor of Secondary Thrombotic Events in High-Risk Patients with Prior Acute Coronary Syndrome – Thrombolysis In Myocardial Infarction (PEGASUS-TIMI 54) trial tested addition of ticagrelor (60mg BD) with asprin vs asprin alone in patients with prior MI. In PAD subgroup ticagrelor resulted in 5.2% absolute risk reduction in CV death, MI, or stoke with significant reduction in both CV & all-cause mortality in patients with PAD & prior MI.

14. The THEMIS studied the same benefit for patients with both symptomatic CAD & PAD. In addition to benefits for MACE, rivaroxabin significantly reduced the secondary endpoint of MALE by approximately 45% with consistent effects for Acute Limb Ischemia (ALI) & major vascular amputation.

15. The VOYGAER PAD trial tested aspirin and rivaroxabin 2.5mg BD vs aspirin alone in a broader PAD population selected only on the basis of symptomatic lower extremity PAD requiring intervention. The combination of aspirin and rivaroxabin was superior to aspirin alone, with a 15% relative risk reduction and 2.6% absolute risk reduction at 3 years. There was a 43% relative increase and 0.78% absolute increase in major bleeding at 3 years but no increase in intracranial hemorrhage or fatal bleeding.

16. The TRA2P-TIMI 50 trial studied vorapaxar , an antagonist of protease-activated receptor 1 (PAR-1), which is the platelet receptor for thrombin, in addition to aspirin and/or clopidogrel , in stable patients with established atherosclerosis. Overall vorapaxar reduced the risk of MI, stroke and CV death but was associated with an increase in moderate or severe bleeding. Benefit was greatest in patients with MI or PAD, whereas there was overall harm in patients with prior stroke. Vorapaxar added to asprin , clopidogrel or DAPT, decreased ALI by 42%.

17. Valvular Heart Diseases - VHD

18. A 65-year-old man with end-stage renal disease, on stable hemodialysis, is diagnosed with atrial  brillation . It is determined that he warrants anticoagulation for stroke prevention. Which of the following agents is labeled by the US Food and Drug Administration for use in patients on hemodialysis? A. Rivaroxaban B. Apixaban C . Dabigatran D . Edoxaban E. None of the above

19. B . The direct thrombin inhibitor dabigatran and the factor Xa inhibitors rivaroxaban , apixaban , and edoxaban are direct oral anticoagulants (DOACs) approved by the US Food and Drug Administration (FDA) for the prevention of stroke in patients with nonvalvular atrial  brillation (AF) and for the treatment of deep venous thrombosis and pulmonary embolism. Each of these agents is in part cleared through renal excretion, and the doses of all four agents must be lowered in patients with reduced creatinine clearance ( CrCl ). Additionally, rivaroxaban , edoxaban , and dabigatran should not be prescribed at all for patients with CrCl less than 15mL/min.1Apixaban has the lowest proportion of renal excretion (25%) among the available DOACs. Its FDA-approved labeling recommends reduced dosage (2.5 mg twice daily, instead of 5 mg twice daily) for patients with AF and serum creatinine greater than 1.5 mg/dL, if the patient also weighs 60 kg (or less), or if age is 80 years or over. Apixaban is also approved for use in hemodialysis (5 mg twice daily, or 2.5 mg twice daily for age ≥80 years or body weight ≤60 kg) based on a small pharmacokinetic study.2In a retrospective observational cohort study comparing apixaban with warfarin in patients with end-stage kidney

20. Which of the following interventions has been shown to reduce the incidence of contrast-induced acute kidney injury after coronary angiography in patients with chronic renal insufciency ? Infusion of 20% mannitol before angiography Administration of atrial natriuretic peptide Normal saline administration before and after angiography Oral administration of N- acetylcysteineE . Low-dose dopamine infusion

21. C Risk factors for contrast-induced acute kidney injury (CI-AKI) include chronic renal insufciency , diabetic nephropathy, intravascular volume depletion, renal artery stenosis, and concurrent use of agents that alter renal hemodynamics (e.g., angiotensin-converting enzyme inhibitors). The smallest possible volume of contrast agent should be used in patients with renal insufciency , because the risk of nephrotoxicity is related to the amount injected.The intervention that has been shown to consistently reduce the incidence of this complication in high-risk patients is intravascular volume expansion with isotonic intravenous (IV)  uids before and after the procedure. A randomized trial of IV isotonic sodium bicarbonate in elective coronary procedures showed no difference in postprocedure CI-AKI compared with IV normal saline, such that either could be used for volume expansion. Several other agents have been evaluated for prevention of CI-AKI, includ

22. A 76-year-old man with hypertension and diabetes is found to have atrial  brillation for the  rst time at a routine ofce visit. He has no history of cardiac symptoms, and an echocardiogram shows normal left ventricular systolic function and no valvular disease or pericardial effusion. His physician initiates dabigatran for long-term anticoagulation. Which of the following statements is TRUE? Anticoagulation is not warranted, because this patient’s risk of thromboembolism is low Dabigatran is an oral factor Xa inhibitor The risk of stroke or systemic embolism is lower with dabigatran 150mg twice daily than with warfarin anticoagulation , with a target international normalized ratio of 2.0 to 3.0 D. Dabigatran 150 mg twice daily increases the risk of hemorrhagic stroke compared with warfarin anticoagulationE . Hepatotoxicity is the major gastrointestinal side effect

23. C . Oral anticoagulation to prevent stroke and other thromboembolic complications is the cornerstone of management of patients with atrial  brillation (AF). This patient is at high risk for thromboembolism in the setting of AF because of his age, hypertension, and diabetes status (CHA2DS2-VASc score = 4). He should therefore be treated with anticoagulation.Dabigatran is an oral direct thrombin inhibitor that reduces the risk of stroke and systemic embolic events (S/SEE) in patients with nonvalvular AF. In the RE-LY trial, dabigatran (at doses of 110 and 150mg twice daily) was compared with warfarin (dose adjusted to achieve an international normalized ratio between 2.0 and 3.0) for the prevention of S/SEE in 18,113 patients with nonvalvular AF, followed for a median of 2 years. The annualized rate of S/SEE was 1.7% with warfarin, 1.5% with the lower-dose dabigatran regimen (P < .001), and 1.1% with the higher-dose regimen (P < .001). The lower-dose dabigatran regimen was noninferior to warfarin, whereas the higher-dose regimen was actually superior to warfarin for S/SEE prevention. The annualized rates of major bleeding were 3.4% with warfarin compared with 2.7% and 3.1% with the lower-dose and higher-dose dabigatran regimens, respectively. That is, the lower-dose dabigatran regimen resulted in less major bleeding than warfarin, whereas bleeding rates were similar in the higher-dose dabigatran and warfarin arms. Importantly , rates of intracranial hemorrhage were signicantly lower in patients randomized to either dose of dabigatran compared with those randomized to warfarin.The most common gastrointestinal side effects of dabigatran are dyspepsia and gastritis; hepatotoxicity was not observed with dabigatran in the RE-LY trial.The labeling for dabigatran recommends a dose adjustment to 75mg twice daily for patients with a reduced cre

24. A 66-year-old man with chronic kidney disease (CKD) is referred for ofce evaluation after a recent admission for an acute coronary syndrome (ACS). Which of the following statements is concerning CKD and cardiovascular disease is TRUE? Patients with CKD are at higher risk of bleeding but at lower risk of thrombotic events compared with normal individuals The outcomes of patients with CKD who present with ACS are similar to those of patients with normal renal function Patients with CKD who present to the hospital with chest pain comprise a relatively low-risk group of ACS patients, with a cardiac event rate of <5% at 30 days There is a graded risk of higher mortality after myocardial infarction in patients with more severe renal dysfunctionE . Uremia is associated with enhanced platelet aggregation

25. D Chronic kidney disease (CKD) identies a patient population at high risk for cardiovascular events, and more severe renal dysfunction is associated with higher risk of adverse cardiovascular outcomes. Up to 40% of all patients with CKD who present to the hospital with chest pain have a cardiac event within 30 days, and patients with end-stage renal disease have the highest mortality after acute myocardial infarction of any large population with chronic disease . Contributors to poor outcomes after acute coronary syndromes in patients with CKD include (1) high prevalence of comorbidities such as diabetes mellitus and heart failure, (2) reduced use of effective therapeutics due to fear of worsening renal dysfunction, (3) therapeutic toxicities , and (4) vascular dysfunction that is exacerbated by renal failure, including a prothrombotic and proinammatory state. Whereas vascular dysfunction contributes to increased rates of coronary thrombosis, uremia is also

26. A 55-year-old obese man (body mass index = 31 kg/m2) with type 2 diabetes mellitus and atrial  brillation is found to have three-vessel coronary disease at angiography and is scheduled for coronary artery bypass graft surgery in 1 week. Which of the following conditions is associated with increased perioperative mortality in this specic patient? A . Male gender B. Timing of surgery C. Atrial  brillation D. Obesity

27. C Factors that signicantly increase mortality with coronary artery bypass graft surgery (CABG) include older age, female sex, emergency surgery, prior CABG, elevated serum creatinine, left ventricular dysfunction, peripheral arterial disease, severe neurologic disease, and chronic obstructive lung disease. Scoring systems including the Society of Thoracic Surgeons risk estimator and the European System for Cardiac Operative Risk Evaluation ( EuroSCORE ) can be used to assess the risk of adverse outcomes in individual patients.1 2 Obesity has not been shown to be an independent predictor of mortality or cerebrovascular accidents after CABG; however, it does predict risk of developing postoperative mediastinitis . Although not included in the EuroSCORE , preoperative atrial  brillation is also associated with increased perioperative mortality and morbidity in patients undergoing cardiac surgery.3