Sadia N Khan

Publications (11)41.08 Total impact

• Article: Stunning and cumulative left ventricular dysfunction occurs late after coronary balloon occlusion in humans insights from simultaneous coronary and left ventricular hemodynamic assessment.

  Stephen P Hoole, Patrick M Heck, Paul A White, Philip A Read, Sadia N Khan, Nick E J West, Michael O'Sullivan, David P Dutka
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  ABSTRACT: We aimed to investigate whether left ventricular (LV) stunning could be detected late after coronary occlusion when coronary flow has normalized. Stunning and cumulative LV dysfunction after ischemia reperfusion has been clearly demonstrated in animal models but has been refuted in several angioplasty models in humans. However, these studies have assessed LV function early, during the reactive hyperemic phase, which might have augmented LV function. We recruited 20 male subjects with single-vessel, type A coronary disease, and normal ventricular function. We simultaneously measured LV function with a conductance catheter and coronary flow velocity with a Combowire (Volcano Therapeutics, Inc., Rancho Cordova, California) at baseline (BL), for 30 s after a low-pressure coronary balloon occlusion for 1 min and again after 30 min, before a second balloon occlusion. Stunning was detected at 30 min after a 1-min balloon occlusion: stroke volume (ml) BL1: 88.4 (22.8) versus BL2: 79.4 (24.0), p = 0.04; tau (ms) BL1: 49.8 (9.0) versus BL2: 52.5 (8.9), p = 0.02, despite full recovery of coronary average peak velocity (p = 0.62). A second balloon occlusion caused cumulative LV dysfunction: stroke volume (ml) BO1: 77.3 (34.6) versus BO2 64.9 (22.9), p = 0.01. Reactive hyperemia significantly augmented early recovery systolic function: dP/dt max 30 s: +5.8% versus 30 min - 5.4%, p = 0.0009. Coronary occlusion for 1-min results in late stunning and cumulative LV dysfunction after 30 min. Reactive hyperemia augments stunned LV systolic function in early recovery.
  04/2010; 3(4):412-8. · 1.07 Impact Factor
• Source

  Available from: Patrick M Heck

  Article: Hyperinsulinemia improves ischemic LV function in insulin resistant subjects.

  Patrick M Heck, Stephen P Hoole, Sadia N Khan, David P Dutka
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  ABSTRACT: Glucose is a more efficient substrate for ATP production than free fatty acid (FFA). Insulin resistance (IR) results in higher FFA concentrations and impaired myocardial glucose use, potentially worsening ischemia. We hypothesized that metabolic manipulation with a hyperinsulinemic euglycemic clamp (HEC) would affect a greater improvement in left ventricular (LV) performance during dobutamine stress echo (DSE) in subjects with IR. 24 subjects with normal LV function and coronary disease (CAD) awaiting revascularization underwent 2 DSEs. Prior to one DSEs they underwent an HEC, where a primed infusion of insulin (rate 43 mU/m 2/min) was co-administered with 20% dextrose at variable rates to maintain euglycemia. At steady-state the DSE was performed and images of the LV were acquired with tissue Doppler at each stage for offline analysis. Segmental peak systolic velocities (Vs) were recorded, as well as LV ejection fraction (EF). Subjects were then divided into two groups based on their insulin sensitivity during the HEC. HEC changed the metabolic environment, suppressing FFAs and thereby increasing glucose use. This resulted in improved LV performance at peak stress, measured by EF (IS group mean difference 5.3 (95% CI 2.5-8) %, p = 0.002; IR group mean difference 8.7 (95% CI 5.8-11.6) %, p < 0.0001) and peak V s in ischemic segments (IS group mean improvement 0.7(95% CI 0.07-1.58) cm/s, p = 0.07; IR group mean improvement 1.0 (95% CI 0.54-1.5) cm/s, p < 0.0001) , that was greater in the subjects with IR. Increased myocardial glucose use induced by HEC improves LV function under stress in subjects with CAD and IR. Cardiac metabolic manipulation in subjects with IR is a promising target for future therapy.
  Cardiovascular Diabetology 01/2010; 9:27. · 3.35 Impact Factor
• Article: Primary coronary microvascular dysfunction and poor coronary collaterals predict post-percutaneous coronary intervention cardiac necrosis.

  Stephen P Hoole, Paul A White, Patrick M Heck, Sadia N Khan, Cameron G Densem, Sarah C Clarke, Leonard M Shapiro, Peter M Schofield, Michael O'Sullivan, David P Dutka
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  ABSTRACT: An elevation in cardiac troponin-I (cTnI) after elective percutaneous coronary intervention (PCI) is because of cardiac necrosis and has prognostic implications. Primary microvascular dysfunction, evident before PCI, and paucity of coronary collaterals at baseline may influence cTnI. We selected 22 patients awaiting elective PCI for a single-vessel, type-A coronary stenosis, with normal left ventricular function and a normal preprocedure cTnI. Intracoronary pressure and Doppler flow were measured during coronary balloon occlusion to derive microvascular resistance: Rp=[Pd(occl)-Pv]/APVoccl and collateral resistance: Rcoll=[Pa-Pd(occl)]/APVoccl, at each stage of PCI, where Pa is mean aortic pressure, Pv is central venous pressure, Pd(occl) is mean distal pressure, Rp is coronary microvascular resistance, Rcoll is coronary collateral resistance, and APVoccl is average peak velocity during coronary balloon occlusion. The resistance indices were compared with postprocedural cTnI levels measured at 24 h. There was a relationship between baseline Rp before PCI and elevated plasma cTnI levels at 24 h. Mean (SEM) Rp (mmHg/cm/s) increased for each cTnI tertile: T1 (mean cTnI 0.04 ng/ml): 1.3 (0.3), T2 (mean cTnI 0.13 ng/ml): 3.1 (0.4), and T3 (mean cTnI 2.5 ng/ml): 4.6 (0.7) (P=0.002). Baseline Rcoll (mmHg/cm/s) was similarly related to cTnI result and mean values showed an increasing trend: T1: 11.1 (1.9), T2: 14.5 (2.3), and T3: 19.5 (3.4) (P=0.12). Serial coronary balloon occlusions did not significantly alter Rp (P=0.82) or recruit coronary collaterals (P=0.69). Primary coronary microvascular dysfunction and poor collaterals at baseline are associated with post-PCI necrosis.
  Coronary artery disease 07/2009; 20(4):253-9. · 1.56 Impact Factor
• Article: Remote ischaemic pre-conditioning does not attenuate ischaemic left ventricular dysfunction in humans.

  Stephen P Hoole, Sadia N Khan, Paul A White, Patrick M Heck, Rajesh K Kharbanda, Cameron G Densem, Sarah C Clarke, Leonard M Shapiro, Peter M Schofield, Michael O'Sullivan, David P Dutka
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  ABSTRACT: Remote ischaemic pre-conditioning (RIPC) reduces distant tissue ischaemia reperfusion injury. We tested the hypothesis that RIPC would protect the left ventricle (LV) from ischaemic dysfunction and stunning. Forty-two patients with single vessel coronary disease and normal LV function were prospectively recruited. Twenty patients had repeated conductance catheter assessment of LV function during serial coronary occlusions with/without RIPC and a further 22 patients underwent serial dobutamine stress echocardiography and tissue Doppler analysis with/without RIPC. Remote ischaemic pre-conditioning was induced by three 5 min inflations of a blood pressure cuff around the upper arm. RIPC did not diminish the degree of ischaemic LV dysfunction during coronary balloon occlusion (Tau, ms: 59.2 (2.8) vs. 62.8 (2.8), P = 0.15) and there was evidence of cumulative LV dysfunction despite RIPC [ejection fraction (EF), %: 54.3 (5.8) vs. 44.9 (3.7), P = 0.03]. Remote ischaemic pre-conditioning did not improve contractile recovery during reperfusion (EF, %: 51.7 (3.6) vs. 51.5 (5.7), P = 0.88 and Tau, ms: 55.6 (2.8) vs. 56.0 (2.0), P = 0.85). A neutral effect of RIPC on LV function was confirmed by tissue Doppler analysis of ischaemic segments at peak dobutamine (V(s), cm s(-1) control: 8.2 (0.4) vs. RIPC 8.1 (0.4), P = 0.43) and in recovery. RIPC does not attenuate ischaemic LV dysfunction in humans.
  European Journal of Heart Failure 06/2009; 11(5):497-505. · 4.90 Impact Factor
• Article: Cardiac Remote Ischemic Preconditioning in Coronary Stenting (CRISP Stent) Study: a prospective, randomized control trial.

  Stephen P Hoole, Patrick M Heck, Linda Sharples, Sadia N Khan, Rudolf Duehmke, Cameron G Densem, Sarah C Clarke, Leonard M Shapiro, Peter M Schofield, Michael O'Sullivan, David P Dutka
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  ABSTRACT: Myocyte necrosis as a result of elective percutaneous coronary intervention (PCI) occurs in approximately one third of cases and is associated with subsequent cardiovascular events. This study assessed the ability of remote ischemic preconditioning (IPC) to attenuate cardiac troponin I (cTnI) release after elective PCI. Two hundred forty-two consecutive patients undergoing elective PCI with undetectable preprocedural cTnI were recruited. Subjects were randomized to receive remote IPC (induced by three 5-minute inflations of a blood pressure cuff to 200 mm Hg around the upper arm, followed by 5-minute intervals of reperfusion) or control (an uninflated cuff around the arm) before arrival in the catheter laboratory. The primary outcome was cTnI at 24 hours after PCI. Secondary outcomes included renal dysfunction and major adverse cardiac and cerebral event rate at 6 months. The median cTnI at 24 hours after PCI was lower in the remote IPC compared with the control group (0.06 versus 0.16 ng/mL; P=0.040). After remote IPC, cTnI was <0.04 ng/mL in 44 patients (42%) compared with 24 in the control group (24%; P=0.01). Subjects who received remote IPC experienced less chest discomfort (P=0.0006) and ECG ST-segment deviation (P=0.005) than control subjects. At 6 months, the major adverse cardiac and cerebral event rate was lower in the remote IPC group (4 versus 13 events; P=0.018). Remote IPC reduces ischemic chest discomfort during PCI, attenuates procedure-related cTnI release, and appears to reduce subsequent cardiovascular events.
  Circulation 02/2009; 119(6):820-7. · 14.74 Impact Factor
• Article: A systematic approach to refractory angina.

  Sadia N Khan, David P Dutka
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  ABSTRACT: Refractory angina pectoris is a common clinical condition associated with significant morbidity and mortality. This review aims to provide a systematic approach to the assessment and treatment of patients with this condition, focusing particularly on recent data. Recent registry-based data have confirmed that a significant proportion of patients referred to cardiologists are suffering from refractory angina pectoris and that this is associated with poor quality of life and increased mortality. A number of novel antianginal drugs have been developed, although there has been little consensus on their use in the treatment of refractory angina. In addition, multiple interventional treatments are available but detailed evaluation is sparse. More recent studies have begun to address some of the major concerns associated with the use of these technologies, including the placebo effect. Studies comparing the different techniques are now beginning to emerge, allowing clinicians and patients to make informed choices. A systematic approach is needed for the assessment and treatment of patients with refractory angina pectoris. Further research must include carefully designed randomized placebo-controlled trials to enable the role and application of the different techniques to be defined.
  Current opinion in supportive and palliative care 01/2009; 2(4):247-51.
• Source

  Available from: Andrew M Crean

  Article: Assessment of Myocardial Scar; Comparison Between F-FDG PET, CMR and Tc-Sestamibi.

  Andrew Crean, Sadia N Khan, L Ceri Davies, Richard Coulden, David P Dutka
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  ABSTRACT: Patients with heart failure and ischaemic heart disease may obtain benefit from revascularisation if viable dysfunctional myocardium is present. Such patients have an increased operative risk, so it is important to ensure that viability is correctly identified. In this study, we have compared the utility of 3 imaging modalities to detect myocardial scar. Prospective, descriptive study. Tertiary cardiac centre. 35 patients (29 male, average age 70 years) with coronary artery disease and symptoms of heart failure (>NYHA class II). Assessment of myocardial scar by (99)Tc-Sestamibi (MIBI), (18)F-flurodeoxyglucose (FDG) and cardiac magnetic resonance (CMR). The presence or absence of scar using a 20-segment model. More segments were identified as nonviable scar using MIBI than with FDG or CMR. FDG identified the least number of scar segments per patient (7.4 +/- 4.8 with MIBI vs. 4.9 +/- 4.2 with FDG vs. 5.8 +/- 5.0 with CMR, p = 0.0001 by ANOVA). The strongest agreement between modalities was in the anterior wall with the weakest agreement in the inferior wall. Overall, the agreement between modalities was moderate to good. There is considerable variation amongst these 3 techniques in identifying scarred myocardium in patients with coronary disease and heart failure. MIBI and CMR identify more scar than FDG. We recommend that MIBI is not used as the sole imaging modality in patients undergoing assessment of myocardial viability.
  Clinical Medicine: Cardiology 01/2009; 3:69-76.
• Article: Assessment of Myocardial Scar; Comparison Between 18F-FDG PET, CMR and 99Tc-Sestamibi

  Crean Andrew, Sadia N Khan, L. Ceri Davies, Coulden Richard, David P Dutka
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  ABSTRACT: Objective: Patients with heart failure and ischaemic heart disease may obtain benefit from revascularisation if viable dysfunctional myocardium is present. Such patients have an increased operative risk, so it is important to ensure that viability is correctly identified. In this study, we have compared the utility of 3 imaging modalities to detect myocardial scar.Design: Prospective, descriptive study.Setting: Tertiary cardiac centre.Patients: 35 patients (29 male, average age 70 years) with coronary artery disease and symptoms of heart failure (>NYHA class II).Intervention: Assessment of myocardial scar by 99Tc-Sestamibi (MIBI), 18F-flurodeoxyglucose (FDG) and cardiac magnetic resonance (CMR).Outcome Measure: The presence or absence of scar using a 20-segment model.Results: More segments were identified as nonviable scar using MIBI than with FDG or CMR. FDG identified the least number of scar segments per patient (7.4 +/- 4.8 with MIBI vs. 4.9 +/- 4.2 with FDG vs. 5.8 +/- 5.0 with CMR, p = 0.0001 by ANOVA). The strongest agreement between modalities was in the anterior wall with the weakest agreement in the inferior wall. Overall, the agreement between modalities was moderate to good.Conclusion: There is considerable variation amongst these 3 techniques in identifying scarred myocardium in patients with coronary disease and heart failure. MIBI and CMR identify more scar than FDG. We recommend that MIBI is not used as the sole imaging modality in patients undergoing assessment of myocardial viability.
  Clinical Medicine : Cardiology. 01/2009;
• Article: Systolic and diastolic dyssynchrony are unaffected by revascularization of viable, dysfunctional myocardium.

  Sadia N Khan, Linda D Sharples, Patrick M Heck, Stephen P Hoole, David P Dutka
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  ABSTRACT: There is little information about change in dyssynchrony with stress or after revascularization. Subjects were recruited to this study if they were referred for revascularization of viable, dysfunctional myocardium. The inclusion criteria were ejection fraction of < or = 35%, sinus rhythm, and QRS duration < or = 120 msec. Tissue Doppler echocardiography with dobutamine stress was performed at baseline and 6 months after revascularization, and dyssynchrony indices (T-sd(c)) were calculated. A total of 25 patients completed a 6-month follow-up. The mean (standard deviation) resting systolic and diastolic T-sd(c) at baseline were 49.3 (18.2) msec and 41.0 (29.4) msec, respectively, with little change during dobutamine stress. After revascularization, there were no significant differences in mean T-sd(c) although there was a modest effect on systolic T-sd(c) at recovery (46.0 [23.1] msec baseline, 34.2 [20.1] msec follow-up, mean difference 11.8 msec, 95% confidence interval 0.3-23.4 msec, P = .046). Resting dyssynchrony in ischemic left ventricular dysfunction does not seem to be altered by dobutamine stress or revascularization.
  Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography 03/2008; 21(3):241-5. · 2.98 Impact Factor
• Source

  Available from: Carol Freeman

  Article: A study to assess changes in myocardial perfusion after treatment with spinal cord stimulation and percutaneous myocardial laser revascularisation; data from a randomised trial.

  Sadia N Khan, Duncan C McNab, Linda D Sharples, Carol J Freeman, Ian Hardy, David L Stone, Peter M Schofield
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  ABSTRACT: Spinal cord stimulation (SCS) and percutaneous myocardial laser revascularisation (PMR) are treatment modalities used to treat refractory angina pectoris, with the major aim of such treatment being the relief of disabling symptoms. This study compared the change in myocardial perfusion following SCS and PMR treatment. Subjects with Canadian Cardiovascular Society class 3/4 angina and reversible perfusion defects as assessed by single-photon emission computed tomographic myocardial perfusion scintigraphy were randomised to SCS (34) or PMR (34). Twenty-eight subjects in each group underwent repeat myocardial perfusion imaging 12 months post intervention. Visual scoring of perfusion images was performed using a 20-segment model and a scale of 0 to 4. The mean (standard deviation) baseline summed rest score (SRS) and stress scores (SSS) were 4.6 (5.7) and 13.6 (9.0) in the PMR group and 6.1 (7.4) and 16.8 (11.6) in the SCS group. At 12 months, SRS was 5.5 (6.0) and SSS 15.3 (11.3) in the PMR group and 6.9 (8.2) and 15.1 (10.9) in the SCS group. There was no significant difference between the two treatment groups adjusted for baseline (p = 1.0 for SRS, p = 0.29 for SSS). There was no significant difference in myocardial perfusion one year post treatment with SCS or PMR.
  Trials 02/2008; 9:9. · 2.02 Impact Factor
• Article: An open label, single-centre, randomized trial of spinal cord stimulation vs. percutaneous myocardial laser revascularization in patients with refractory angina pectoris: the SPiRiT trial.

  Duncan McNab, Sadia N Khan, Linda D Sharples, Judy Y Ryan, Carol Freeman, Noreen Caine, Sue Tait, Ian Hardy, Peter M Schofield
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  ABSTRACT: Refractory angina pectoris leads to significant morbidity. Treatment options include percutaneous myocardial laser revascularization (PMR) and spinal cord stimulation (SCS). This study was designed to compare these two treatments. Subjects with Canadian Cardiovascular Society (CCS) class 3/4 angina and reversible perfusion defects were randomized to SCS (34) or PMR (34). The primary outcome was to compare exercise treadmill time on a modified Bruce protocol over 12 months. Thirty subjects in both groups completed 12-month follow-up. The mean total exercise time was 6.38 +/- 3.45 min in the SCS group and 7.41+/-3.68 min in the PMR group at baseline and 7.08 +/- 0.67 min in the SCS group and 7.12 +/-0.71 min in the PMR group at 12 months (95% confidence limits for the difference between the groups -1.02 to + 2.2 min, P = 0.466). There were no differences in angina-free exercise capacity, CCS class, and quality of life between treatments. SCS patients had more adverse events in the first 12 months, mainly angina or SCS system related (P = 0.001). There was little evidence of a difference in effectiveness between SCS and PMR in patients with refractory angina.
  European Heart Journal 06/2006; 27(9):1048-53. · 10.48 Impact Factor