Sohail Ikram

Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial.

BACKGROUND c-kit-positive, lineage-negative cardiac stem cells (CSCs) improve post-infarction left ventricular (LV) dysfunction when administered to animals. We undertook a phase 1 trial (Stem Cell Infusion in Patients with Ischemic cardiOmyopathy [SCIPIO]) of autologous CSCs for the treatment of heart failure resulting from ischaemic heart disease. METHODS In stage A of the SCIPIO trial, patients with post-infarction LV dysfunction (ejection fraction [EF] ≤40%) before coronary artery bypass grafting were consecutively enrolled in the treatment and control groups. In stage B, patients were randomly assigned to the treatment or control group in a 2:3 ratio by use of a computer-generated block randomisation scheme. 1 million autologous CSCs were administered by intracoronary infusion at a mean of 113 days (SE 4) after surgery; controls were not given any treatment. Although the study was open label, the echocardiographic analyses were masked to group assignment. The primary endpoint was short-term safety of CSCs and the secondary endpoint was efficacy. A per-protocol analysis was used. This study is registered with ClinicalTrials.gov, number NCT00474461. FINDINGS This study is still in progress. 16 patients were assigned to the treatment group and seven to the control group; no CSC-related adverse effects were reported. In 14 CSC-treated patients who were analysed, LVEF increased from 30·3% (SE 1·9) before CSC infusion to 38·5% (2·8) at 4 months after infusion (p=0·001). By contrast, in seven control patients, during the corresponding time interval, LVEF did not change (30·1% [2·4] at 4 months after CABG vs 30·2% [2·5] at 8 months after CABG). Importantly, the salubrious effects of CSCs were even more pronounced at 1 year in eight patients (eg, LVEF increased by 12·3 ejection fraction units [2·1] vs baseline, p=0·0007). In the seven treated patients in whom cardiac MRI could be done, infarct size decreased from 32·6 g (6·3) by 7·8 g (1·7; 24%) at 4 months (p=0·004) and 9·8 g (3·5; 30%) at 1 year (p=0·04). INTERPRETATION These initial results in patients are very encouraging. They suggest that intracoronary infusion of autologous CSCs is effective in improving LV systolic function and reducing infarct size in patients with heart failure after myocardial infarction, and warrant further, larger, phase 2 studies. FUNDING University of Louisville Research Foundation and National Institutes of Health.

Prediction of Hypertension Improvement After Stenting of Renal Artery Stenosis: Comparative Accuracy of Translesional Pressure Gradients, Intravascular Ultrasound, and Angiography

OBJECTIVES We investigated the comparative accuracy of renal translesional pressure gradients (TPG), intravascular ultrasound (IVUS), and angiographic parameters in predicting hypertension improvement after stenting of renal artery stenosis (RAS). BACKGROUND The degree of RAS that justifies stenting is unknown. METHODS In 62 patients with RAS, TPG (resting and hyperemic systolic gradient [HSG], fractional flow reserve, and mean gradient) were measured by a pressure guidewire; IVUS and angiographic parameters (minimum lumen area and diameter, area stenosis, and diameter stenosis) were measured by quantitative analyses. RESULTS The HSG had a larger area under the curve than most other parameters and an HSG >or=21 mm Hg had the highest sensitivity, specificity, and accuracy (82%, 84%, and 84%, respectively) in predicting hypertension improvement after stenting of RAS. The average IVUS area stenosis was markedly greater in RAS with an HSG >or=21 mm Hg versus <21 mm Hg (78% vs. 38%, respectively; p < 0.001). After stenting, hypertension improved in 84% of patients with an HSG >or=21 mm Hg (n = 36) versus 36% of patients with an HSG <21 mm Hg (n = 26) at 12 months, p < 0.01; the number of antihypertensive medications was significantly lower in patients with an HSG >or=21 mm Hg versus <21 mm Hg (2.30 +/- 0.90 vs. 3.40 +/- 0.50, respectively; p < 0.01). By multivariable analysis, HSG was the only independent predictor of hypertension improvement (odds ratio: 1.39; 95% confidence interval: 1.05 to 1.65; p = 0.013). CONCLUSIONS An HSG >or=21 mm Hg provided the highest accuracy in predicting hypertension improvement after stenting of RAS, suggesting that an HSG >or=21 mm Hg is indicative of significant RAS.

Increased Risk of Adverse Neurocognitive Outcomes With Proprotein Convertase Subtilisin-Kexin Type 9 Inhibitors.

Background— There is encouraging evidence of the efficacy of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors; however, their long-term safety remains unclear. We performed a meta-analysis of studies to evaluate the long-term safety of PCSK9 inhibitors. Methods and Results— Our search strategy yielded 11 studies (9 smaller early-phase and 2 larger outcome trials). The outcomes assessed were cumulative serious adverse events, musculoskeletal adverse events, neurocognitive adverse events, and stroke. Odds ratio (OR) was calculated using the Mantel–Haenszel method. Subgroup analysis was done to assess the difference in safety between the smaller early-phase studies and the larger outcome studies. Our meta-analysis suggested no difference in the incidence of serious adverse events (OR, 1.00; 95% confidence interval [CI], 0.88−1.15), musculoskeletal adverse events (OR, 1.01; 95% CI, 0.87−1.13), neurocognitive adverse events (OR, 1.29; 95% CI, 0.64−2.59), or stroke (OR, 1.44; 95% CI, 0.57−3.65) with the use of PCSK9 inhibitors. Subgroup analysis of the 2 large outcome studies did suggest an increased incidence of neurocognitive adverse events (OR, 2.85; 95% CI, 1.34−6.06) with the use of PCSK9 inhibitors. However, the overall incidence of neurocognitive adverse events and stroke was <1%, whereas the cumulative incidence of serious adverse events and musculoskeletal events was >10% in both the groups. Conclusions— Our analysis suggests that PCSK9 inhibitors are not associated with an increased risk of cumulative severe adverse effects, musculoskeletal effects, or stroke. There is a signal toward adverse neurocognitive effects, seen in the outcome studies with a larger sample size and longer follow-up. There should be close monitoring, for the increased risk of neurocognitive events in the ongoing outcome studies and post-marketing surveillance.

Thirty-Day Readmission Rate and Costs After Percutaneous Coronary Intervention in the United States: A National Readmission Database Analysis

Background— The association of short-term readmissions after percutaneous coronary intervention (PCI) on healthcare costs has not been well studied. Methods and Results— The Healthcare Cost and Utilization Project National Readmission Database encompassing 722 US hospitals was used to identify index PCI cases in patients ≥18 years old. Hierarchical regression analyses were used to examine the factors associated with risk of 30-day readmission and higher cumulative costs. We evaluated 206 869 hospitalized patients who survived to discharge after PCI from January through November 2013 and analyzed readmissions over 30 days after discharge. A total of 24 889 patients (12%) were readmitted within 30 days, with rates ranging from 6% to 17% across hospitals. Among the readmitted patients, 13% had PCI, 2% had coronary artery bypass surgery, and 3% died during the readmission. The most common reasons for readmission included nonspecific chest pain/angina (24%) and heart failure (11%). Mean cumulative costs were higher for those with readmissions (

Effects of Nifedipine and Nitroglycerin on Left Ventricular Systolic Dysfunction and Impaired Diastolic Filling After Exercise-Induced Ischemia in Humans

39 634 versus

Fluoroscopy-guided thrombolysis of mechanical mitral valve thrombosis in a young female with antiphospholipid antibody syndrome

22 058; P<0.001). The multivariable analyses showed that readmission increased the log10 cumulative costs by 45% (&bgr;: 0.445; P<0.001). There was no significant difference in cumulative costs by the type of insurance. Conclusions— In a national sample of inpatient PCI cases, 30-day readmissions were associated with a significant increase in cumulative costs. The majority of readmissions were because of low-risk chest pain that did not require any intervention. Ongoing effort is warranted to recognize and mitigate potentially preventable post-PCI readmissions.

The Macklin effect causing a pneumopericardium.

OBJECTIVES This study sought to determine whether calcium antagonist, compared with nitroglycerin, administration attenuates left ventricular dysfunction after exercise-induced ischemia in humans. BACKGROUND Exercise-induced ischemia impairs left ventricular systolic function and diastolic filling after exercise. The mechanism of this phenomenon is unknown but may relate to intracellular calcium overload. METHODS Echocardiography was performed in 131 patients before and 30 min, 2 h and 4 h after exercise stress test. Ischemia was defined as a reversible thallium stress defect. No medication, sublingual nitroglycerin or nifedipine was randomly given to each patient at peak exercise. RESULTS Isovolumetric relaxation time was significantly prolonged from rest (100 +/- 19 ms [mean +/- SD]) to 30 min (118 +/- 20 ms, p < 0.0005), 2 h (117 +/- 18 ms, p < 0.0005) and 4 h (110 +/- 22 ms, p < 0.05) after exercise in 21 patients with exercise-induced ischemia who received no medication (ischemia-none group). Isovolumetric relaxation time similarly increased after exercise in 23 patients who received nitroglycerin and had exercise-induced ischemia (ischemia-NTG group) but was unchanged in 20 patients with exercise-induced ischemia who received nifedipine (ischemia-nifedipine group). Peak early filling velocity decreased in the ischemia-none and ischemia-NTG groups from rest to 30 min and 2 h after exercise, but peak early filling velocity was unchanged in the ischemia-nifedipine group. Ejection fraction decreased from rest to 30 min after exercise in the ischemia-none group (59 +/- 12% vs. 51 +/- 13%, p < 0.025) and ischemia-NTG group (59 +/- 14% vs. 49 +/- 14%, p < 0.005) but was unchanged in the ischemia-nifedipine group (60 +/- 19% vs. 64 +/- 18%, p = NS). A new regional left ventricular wall motion abnormality occurred more frequently 30 min after exercise in the ischemia-none group (11 [52%] of 21) and ischemia-NTG group (9 [39%] of 23) compared with the ischemia-nifedipine group (2 [10%] of 20, both p < 0.05). No change occurred in left ventricular systolic function and diastolic filling after exercise in the control groups. CONCLUSIONS Exercise-induced ischemia impairs systolic function and diastolic filling after exercise. Sublingual nifedipine but not nitroglycerin attenuates this process and suggests that altered calcium homeostasis may play a role in left ventricular dysfunction that occurs after exercise-induced ischemia.

Invasive Imaging in Critical Limb Ischemia

Prosthetic valve thrombosis (PVT) is a rare but potentially fatal complication of mechanical valve prosthesis. The differential diagnoses for prosthetic valve obstruction includes pannus formation, prosthetic valve dehiscence, prosthetic valve endocarditis, chordae entrapment, patient-prosthesis mismatch and primary device failure. Establishing a diagnosis requires an understanding of prosthetic valve haemodynamics and careful correlation of clinical and imaging findings. Definitive therapy must be individualised based on various patient-specific factors. We present a case of mechanical mitral PVT in a young woman with antiphospholipid antibody syndrome, and outline the diagnostic and therapeutic approach utilised for successful treatment. The success and complication rates of various therapeutic strategies are also discussed, and highlight the need for individualised decision-making rather than a one-size-fits-all approach to PVT.

Angina caused by a giant coronary artery fistula

Pleuropericarditis is a common clinical entity that has been reported in association with several diseases. However, pleuropericarditis following blunt thoracic trauma is very rare and difficult to diagnose. Here we present a case of a young man who presented to the emergency department with acute shortness of breath following a motor vehicle accident. He was found to have a pleuro-pericardial communication worsened by barotrauma, resulting in tension pneumopericardium.

CRT-161 Utility of Clinical Risk Scoring Systems in Predicting Long Term Outcome After Percutaneous Coronary Intervention in a Veterans Affairs Medical Center

Critical limb ischemia (CLI) refers to a condition with markedly reduced blood flow to the extremities due to severe obstruction of the arteries and is characterized by chronic ischemic at-rest pain, ulcers, or gangrene in one or both extremities and objectively proven arterial occlusive disease. The incidence of CLI is approximately 500–1000 per million year, with the highest rates among older subjects, smokers, and diabetics. It remains one of the common causes of primary amputation. CLI has a significant impact on the quality of life and carries a grim prognosis both in terms of limb salvage and survival and is a critical public health issue. Invasive and noninvasive modalities are now available to diagnose critical limb ischemia. Iodine-based contrast angiography still remains the gold standard. Among patients with limited renal reserve CO2 angiography offers a viable option.