Ischemia Trial: Does the Cardiology Community Need to Pivot or Continue Current Practices?

PURPOSE OF REVIEW: For decades, the standard of care for stable ischemic heart disease (SIHD) has been an ischemia-centric approach based on largely observational data suggesting a survival benefit of revascularization in patients with moderate-or-severe ischemia. In this article, we will objectively review the evolution of the ischemia paradigm, the trial evidence comparing revascularization to medical therapy in SIHD, and what contemporary practice should be in 2022. RECENT FINDINGS: Randomized trials, including COURAGE and, most recently, the ISCHEMIA trial, have shown no reduction in "hard outcomes" like death and myocardial infarction (MI) in SIHD compared to medical therapy. The trial excluded high-risk patients with left main disease, low ejection fraction (EF) < 35%, and severe unacceptable angina. Irrespective of the severity of ischemia and the extent of coronary artery disease (CAD), revascularization did not offer any prognostic advantage over medical therapy. On the other hand, there was a durable improvement in symptoms. While there are many caveats to the ISCHEMIA trial, the overall strengths of the trial outweigh these limitations. The findings of ISCHEMIA are consistent with previous trials. It is time for the cardiology community to pivot towards medical therapy as the initial step for most patients with SIHD. Physicians should have the "COURAGE" to embrace "ISCHEMIA" and be comfortable with treating ischemia medically.

High-Risk "Protected" Percutaneous Coronary Intervention with Mechanical Circulatory Support in a Non-Surgical Center - An Early Asian Experience.

High-risk "protected" percutaneous coronary intervention (PCI) using mechanical circulatory support (MCS) devices, particularly the Impella axial pump, has emerged as a viable treatment option for high-risk patients with satisfactory clinical outcomes. High-risk and complex interventions have mostly remained within the domain of surgical centers. We report on an early "protected" PCI experience using MCS with the Impella flow pump at a high-volume PCI hospital without on-site surgery. A total of 5 patients underwent elective "protected" PCI utilizing MCS with Impella at our institution. The mean left ventricular ejection fraction was 28 ± 10% and all patients had triple vessel coronary artery disease with the majority having a high SYNTAX score. Device implantation and procedural success were achieved in all cases with no intraprocedural or access site complications. All patients were alive at 30 days and clinically well. The Impella unloads the ventricle, improves forward cardiac output and lowers myocardial oxygen demand, thereby improving mean arterial pressure and coronary perfusion. Device insertion is relatively quick and the "learning curve" is short, centering mainly around managing large bore access. Our limited experience suggests that not only is high-risk PCI with Impella support feasible in a non-surgical center, but that it may be crucial to enable success.

Drug-Coated Balloons: A Safe and Effective Alternative to Drug-Eluting Stents in Small Vessel Coronary Artery Disease.

BACKGROUND: Drug-coated balloons (DCB) have been used to treat de novo small vessel coronary disease (SVD), with promising results and shorter dual antiplatelet therapy (DAPT) duration compared to drug-eluting stents (DES). We compared safety and effectiveness of the two treatments at 1 year. METHODS: We reviewed 3,613 angioplasty cases retrospectively from 2011 to 2013 and identified 335 patients with SVD treated with device diameter of ≤2.5 mm. DCB-only angioplasty was performed in 172 patients, whereas 163 patients were treated with second-generation DES. RESULTS: DCB patients had smaller reference vessel diameter (2.22 ± 0.30 vs. 2.44 ± 0.19 mm, P < 0.001) and received smaller devices (median diameter 2.25 vs. 2.50 mm, P < 0.001) compared to the DES group. DES-treated vessels had larger acute lumen gain (1.71 ± 0.48 mm) than DCB (1.00 ± 0.53 mm, P < 0.001). Half the patients had diabetes mellitus. While there were more patients presenting with acute coronary syndrome (ACS) in the DCB group (77.9% vs. 62.2%, P = 0.013), they received shorter DAPT (7.4 ± 4.7 vs. 11.8 ± 1.4 months, P < 0.001) than the DES group. The 1-year composite major adverse cardiac event rate was 11.6% in the DCB arm and 11.7% in the DES arm (P = 1.000), with target lesion revascularization rate of 5.2% and 3.7%, respectively, (P = 0.601). CONCLUSIONS: In this high-risk cohort of patients, DCB-only angioplasty delivered good clinical outcome at 1 year. The results were comparable with DES-treated patients, but had the added benefit of a shorter DAPT regime.

Drug coated balloon angioplasty in elderly patients with small vessel coronary disease.

BACKGROUND: Coronary angioplasty in advanced age is associated with higher rate of comorbidities and complications. Drug coated balloon only angioplasty (DCBA) has emerged as an alternative to treat small vessel coronary disease (SVCD), of reference vessel diameters <2.8 mm, with shorter duration of dual antiplatelet (DAPT). This is the first study to assess the DCBA efficacy in an elderly population with SVCD. METHODS AND RESULTS: We performed a prospective study of 447 patients (334 patients aged <75 and 113 patients aged ⩾75 years old) acquired from the SeQuent Please Small Vessel 'Paclitaxel-Coated Balloon Only' registry. In the older age group, more patients have hypertension (89% versus 77%; p = 0.006), renal insufficiency (21% versus 6%; p < 0.001), atrial fibrillation (17% versus 7%; p = 0.001), and calcified lesions (33% versus 20%; p = 0.006). At 30 days, there was one myocardial infarction requiring target lesion revascularization (TLR) in the younger group. No major adverse cardiac event (MACE) was observed in the older group. At 9 months, the MACE rate in the younger group was 4.2% and 6.1% in the older group (p = 0.453), with TLR rates at 3.9% and 3.0% (p = 0.704) respectively. There was no cardiac death observed. CONCLUSION: DBCA in the elderly with SVCD is as safe and effective compared with younger patients despite more complex anatomy and comorbidities.

Rheolytic thrombectomy in patients with massive pulmonary embolism: a report of two cases and review of literature.

We present two cases of massive pulmonary embolism with persistent systolic hypotension but both have contraindications for thrombolysis. Therefore, rheolytic thrombectomy using AngioJet was performed and immediate haemodynamic improvement was achieved including blood pressure and symptoms. According to guidelines, catheter embolectomy or fragmentation may be considered as alternative to surgical treatment in massive pulmonary embolism patients when thrombolysis is absolutely contraindicated or has failed. Percutaneous catheter-based interventional techniques include thrombus fragmentation, rheolytic thrombectomy, suction thrombectomy and rotational thrombectomy. With the existing literature review and our case, rheolytic thrombectomy for treatment of massive pulmonary embolism using AngioJet achieves a high procedural success rate (approximately 90%) n terms of improvement of haemodynamics, pulmonary perfusion and angiographic result but low complication rate.

Clinical outcomes of intracoronary eptifibatide bolus only versus intracoronary bolus and intravenous infusion of eptifibatide in primary percutaneous coronary intervention.

Intracoronary bolus of eptifibatide during percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) has been shown to result in higher local platelet glycoprotein IIb/IIIa receptor occupancy with improved microvascular perfusion. It is unclear whether intracoronary administration of eptifibatide in a larger patient population results in favourable clinical outcomes. We evaluated the safety and efficacy of two regimens of intracoronary eptifibatide (bolus only versus bolus followed by intravenous infusion) in patients undergoing primary PCI for ST-elevation MI. They were divided into two groups: Group A (n=67) who received fixed-dose intracoronary eptifibatide bolus only and Group B (n=88) who received intracoronary bolus and continuous intravenous infusion of eptifibatide for 18 h. The preliminary findings from our registry showed that both regimens were associated with good angiographic outcomes, few bleeding events and low in-hospital major adverse cardiac events. A large prospective randomized, multi-centre trial is needed to confirm our observation.

Vanishing platelets: rapid and extreme tirofiban-induced thrombocytopenia after percutaneous coronary intervention for acute myocardial infarction.

Glycoprotein IIb/IIIa inhibitors are established treatment for patients who develop acute coronary syndromes. Thrombocytopenia is known to occur following the administration of various drugs, including heparin and glycoprotein IIb/IIIa inhibitors. In the case of glycoprotein IIb/IIIa inhibitors, the mechanism is thought to be drug-dependent antibodies. In most cases, the thrombocytopenia is mild or moderate in severity. Severe thrombocytopenia (platelet count, <50 x 10(9)/L) is distinctly rare. Herein, we report a case of tirofiban-induced thrombocytopenia in which the overall platelet count dropped precipitously to <1 x 10(9)/L within 12 hours of administration; recovery was relatively prolonged, possibly owing to concomitant renal insufficiency. The severity and the rapidity of onset emphasize the need to routinely check platelet counts early after tirofiban administration, in order to prevent sequelae.

Community-based interventions to promote blood pressure control in a developing country: a cluster randomized trial.

BACKGROUND: Despite convincing evidence that lowering blood pressure decreases cardiovascular morbidity and mortality, the hypertension burden remains high and control rates are poor in developing countries. OBJECTIVE: To assess the effectiveness of 2 community-based interventions on blood pressure in hypertensive adults. DESIGN: Cluster randomized, 2 x 2 factorial, controlled trial. (ClinicalTrials.gov registration number: NCT00327574) SETTING: 12 randomly selected communities in Karachi, Pakistan. PATIENTS: 1341 patients 40 years or older with hypertension (systolic blood pressure >or=140 mm Hg, diastolic blood pressure >or=90 mm Hg, or already receiving treatment). MEASUREMENTS: Reduction in systolic blood pressure from baseline to end of follow-up at 2 years. INTERVENTION: Family-based home health education (HHE) from lay health workers every 3 months and annual training of general practitioners (GPs) in hypertension management. RESULTS: The age, sex, and baseline blood pressure-adjusted decrease in systolic blood pressure was significantly greater in the HHE and GP group (10.8 mm Hg [95% CI, 8.9 to 12.8 mm Hg]) than in the GP-only, HHE-only, or no intervention groups (5.8 mm Hg [CI, 3.9 to 7.7 mm Hg] in each; P < 0.001). The interaction between the main effects of GP training and HHE on the primary outcome approached significance (interaction P = 0.004 in intention-to-treat analysis and P = 0.044 in per-protocol analysis). LIMITATIONS: Follow-up blood pressure measurements were missing for 22% of patients. No mechanism was detected by which interventions lowered blood pressure. CONCLUSION: Family-based HHE delivered by trained lay health workers, coupled with educating GPs on hypertension, can lead to significant blood pressure reductions among patients with hypertension in Pakistan. Both strategies in combination may be feasible for upscaling within the existing health care systems of Indo-Asian countries. PRIMARY FUNDING SOURCE: Wellcome Trust.

Results of a cross-sectional survey about lipid-management practices among cardiologists in Pakistan: assessment of adherence to published treatment guidelines.

OBJECTIVES: The aims of this study were to assess how closely cardiologists in Pakistan followed published recommendations for lipid management and to identify the factors associated with such behavior. METHODS: A cross-sectional survey was delivered in person between September and December 2007 to all cardiologists practicing in 4 major cities in Pakistan (Karachi, Lahore, Quetta, and Peshawar). A standard questionnaire was used to obtain information from cardiologists. Adherence to the guidelines established by the 2004 National Cholesterol Education Program Adult Treatment Panel III was computed based on answers to 14 questions; each correct answer (ie, the answer that followed the guidelines) was assigned 1 point, for a maximum cumulative score of 14. Multivariable linear regression was performed to determine the factors independently associated with guideline knowledge. RESULTS: A total of 295 cardiologists were approached; 239 consented to participate (overall response rate, 81.0%). The median score was 9 out of a maximum of 14 (interquartile range, 8-11). There were important points of divergence from practice recommendations, including suboptimal targets for low-density lipoprotein cholesterol (LDL-C) (< or = 70 mg/dL was the target used by only 16.7% of respondents [40/239]), undertreatment of revascularized patients (31.4% [75/239]), cessation of statin therapy once LDL-C targets were achieved (20.9% [50/239]), and use of different treatment thresholds for patients aged >65 years (41.8% [100/239]) and female patients (46.4% [111/239]). In the adjusted analysis, experienced physicians, interventional cardiologists, and those who pursued continuing medical education activities (journals and conferences) had higher scores (P = 0.005, P = 0.041, P = 0.008, and P = 0.001, respectively). CONCLUSION: We found important self-reported departures from recommended lipid-management guidelines among cardiologists in Pakistan.

Disproportionately high risk of left ventricular hypertrophy in Indo-Asian women: a call for more studies.

OBJECTIVE: Indo-Asians have one of the highest rates of cardiovascular disease worldwide. Estimates and determinants of left ventricular hypertrophy (LVH) in this population are not known. We sought to determine the prevalence of and risk factors for LVH in Karachi, Pakistan. METHODS: We conducted a population-based cross-sectional study on 320 randomly selected adults from the general population aged 40 years or above. LVH was defined as increased left ventricular mass index (LVMI) on echocardiogram (>115 g/m(2) in men and >95 g/m(2) in women) employing the adjusted Devereux equation. Multivariable models were built and logistic regression analysis was done for the primary outcome of LVH. RESULTS: Mean age of subjects was 52.7 (10.4) years, 50% were women. Mean LVMI (SD) was 72.0 (19.2) [median 71.1] g/m(2) in men and 75.7 (25.9) [median 72.9] g/m(2) in women. The overall prevalence of LVH was 21.9% in women and 2.5% in men (P < 0.001). The factors (odds ratio, 95% CI) independently associated with LVH were women versus men (11.35, 3.79-34.02), systolic blood pressure > versus

Intramyocardial hematoma after coronary perforation during percutaneous coronary intervention--anticipated and treated.

Coronary perforation is an uncommon complication of percutaneous coronary intervention and the subset of patients developing a subepicardial hematoma without hemopericardium is even rarer. Subepicardial (or intramyocardial) hematomas are often associated with catastrophic events. These hematomas are reported mainly in those with prior coronary artery bypass grafting (CABG). To date, only 2 cases have been reported in non-CABG patients. Ours is such a case where the perforation failed to resolve. Despite the absence of pericardial effusion or hemodynamic instability, we anticipated the possibility of a dissecting myocardial hematoma and proceeded with preemptive surgery. Perioperative findings confirmed the presence of a large intramyocardial hematoma, conservative treatment of which may well have led to potentially lethal consequences. We then review the scant literature on the subject.

Pacemaker-mediated tachycardia induced by left ventriculography during diagnostic catheterisation: a rare event.

Pacemaker-mediated tachycardia (PMT) is an arrhythmia seen in patients implanted with dual-chamber pacemakers. It occurs when ventricular contraction is followed by retrograde conduction to the atrium, which is sensed by the pacemaker, leading to ventricular triggering. A vicious re-entry cycle is set up, leading to incessant tachycardia unless appropriately terminated. A common precipitant is a premature ventricular contraction (PVC). Although PVCs are frequently generated during ventriculography, PMT is an extremely rare event during cardiac catheterisation despite the fact that a large number of patients with implanted pacemakers do undergo the procedure. We report on a case and hope to highlight the possibility of PMT occurring during catheterisation, as well on therapeutic options.

Survival of patients receiving fibrinolytic therapy for acute ST-segment elevation myocardial infarction in a developing country - patient characteristics and predictors of mortality.

There is paucity of outcomes data on patients receiving fibrinolytic therapy (FT) for acute ST-elevation myocardial infarction (STEMI) in Indo-Asians. We conducted this study to determine survival as well as correlates of mortality in this population. Hospital charts of 230 patients receiving FT for acute STEMI between January 2002 and December 2004 were reviewed. Primary outcome variable was total mortality. Cox proportional hazards regression models were constructed. At a median follow-up of 717 days, 13.5% died, majority (23) during the in-hospital period. Multivariate predictors of mortality included (adjusted hazards ratio [HR], 95% confidence interval [CI]) age (HR 1.06, 95% CI 1.01-1.13), ejection fraction (HR 0.93, 95% CI 0.89-0.97), admission white cell count (HR 1.02, 95% CI 1.01-1.04) and change in ST-segment elevation (HR 0.96, 95% CI 0.92-0.99). We conclude that patients receiving FT for acute STEMI in Pakistan are a relatively high-risk group with a 10% in-hospital mortality and high frequency of recurrent events. Comparison data with primary angioplasty as an alternative strategy are needed.

Prognosis of hospitalized new-onset systolic heart failure in Indo-Asians--a lethal problem.

BACKGROUND: Systolic heart failure (SHF), particularly when requiring hospital admission carries a poor prognosis. There is a paucity of data in Indo-Asians on outcomes of SHF, among whom the burden of cardiovascular disease is consistently rising. The purpose of this study was to determine the frequency and predictors of mortality and morbidity amongst patients admitted with new-onset SHF at a tertiary care hospital in Pakistan. METHODS AND RESULTS: Hospital charts of 196 patients with a diagnosis of new or recent onset (<3 months) SHF (ejection fraction [EF] <40%) were reviewed. Patients who died during the admission, those with life-limiting concomitant disease, and those without follow-up were excluded. Survival was calculated according to the Kaplan-Meier method. Hazards ratios (HR) and 95% confidence intervals (CI) were calculated using Cox's regression model. Mean age (SD) was 61 (12.8) years. Majority (77%) had a prior ischemic heart disease. Mean EF (SD) was 25% (8.7). Median follow-up period was 379 days. Fifty-four (27.5%) patients died (at least 12 [22.2%] sudden deaths) and 102 (52%) experienced combined event of death or repeat hospitalization for SHF. Factors independently associated with death included (HR [95% CI]), serum sodium (0.94 [0.90-0.97]), admission pulse (1.02 [1.01-1.04]), systolic blood pressure (0.98 [0.97-0.99]), and severe mitral regurgitation (1.90 [1.03-3.48]). CONCLUSIONS: Admission for new or recent onset SHF predicts a grave 1-year prognosis in Indo-Asians. Measures to prevent ischemic heart disease and its sequelae are essential because developing nations simply cannot afford to treat and manage heart failure.

Outcomes of primary percutaneous coronary intervention at a joint commission international accredited hospital in a developing country -- can good results, possibly similar to the west, be achieved?

BACKGROUND: Primary percutaneous coronary intervention (PCI) is the treatment of choice following ST-elevation myocardial infarction (STEMI). There is limited adoption and a paucity of data on outcomes following primary PCI in developing countries. The objective of this study was to describe the procedural and clinical outcomes of patients undergoing PCI for STEMI at a Joint Commission International Accreditation (JCIA) certified hospital in Pakistan and make a comparison with outcomes from the West. METHODS: We conducted a retrospective cohort study at a tertiary care university hospital in Karachi, Pakistan. A total of 277 consecutive patients undergoing primary PCI between January 2001 and December 2005 were reviewed. Exclusion criteria included preceding fibrinolytic therapy and STEMI due to stent thrombosis. Cox proportional hazards models were constructed. The primary outcome was mortality. RESULTS: Procedural success was 97.1%. Inhospital mortality was 8.3% (43.9% in cardiogenic shock, 2.1% in non-shock patients), comparing very favorably with the published literature from developed countries. Multivariate predictors of death included (hazards ratio, 95% confidence interval) age (1.42 [1.14-1.76]), mechanical ventilation (8.35 [2.82-24.73]), cardiogenic shock (2.80 [1.04-7.55]), prior CABG (9.78 [1.15-83.13]) and ejection fraction (0.96 [0.92-0.99]). CONCLUSIONS: We conclude that excellent outcomes for a critical illness like STEMI can be achieved in a developing country at a JCIA-certified hospital, possibly similar to those seen in the West. There is a strong need for making the practice of primary PCI more widespread in developing nations. More outcomes data are needed from similar hospitals in the region to determine whether our results are generalizable.

High prevalence of lack of knowledge of symptoms of acute myocardial infarction in Pakistan and its contribution to delayed presentation to the hospital.

BACKGROUND: We conducted an observational study to determine the delay in presentation to hospital, and its associates among patients experiencing first Acute Myocardial Infarction (AMI) in Karachi, Pakistan. METHODS: A hospital based cross-sectional study was conducted at National Institute of Cardiovascular Disease (NICVD) in Karachi. A structured questionnaire was used to collect data. The primary outcome was delay in presentation, defined as a time interval of six or more hours from the onset of symptoms to presentation to hospital. Logistic regression analysis was performed to determine the factors associated with prehospital delay. RESULTS: A total of 720 subjects were interviewed; 22% were females. The mean age (SD) of the subjects was 54 (+/- 12) years. The mean (SE) and median (IQR) time to presentation was 12.3 (1.7) hours and 3.04 (6.0) hours respectively. About 34% of the subjects presented late. Lack of knowledge of any of the symptoms of heart attack (odds ratio (95% CI)) (1.82 (1.10, 2.99)), and mild chest pain (10.05 (6.50, 15.54)) were independently associated with prehospital delay. CONCLUSION: Over one-third of patients with AMI in Pakistan present late to the hospital. Lack of knowledge of symptoms of heart attack, and low severity of chest pain were the main predictors of prehospital delay. Strategies to reduce delayed presentation in this population must focus on education about symptoms of heart attack.

The "incidental" episode of ventricular fibrillation: a case report.

Polymorphic ventricular tachycardia and ventricular fibrillation (VF) carry important prognostic implications, especially in the post myocardial infarction period. However, artifact on the electrocardiographic tracing can mimic VF particularly on routinely recorded rhythm strips in hospitals. Such misinterpretation can lead to expensive (and potentially risky) diagnostic and therapeutic steps. We report on such a case and highlight the need for careful inspection of the tracing.