Freny Vaghaiwalla Mody

Prognostic significance of silent myocardial ischemia in patients with unstable angina

Silent myocardial ischemia is common in unstable angina, but its prognostic significance is unknown. Fifty-two (42 with subsequent angiography) of 81 patients prospectively evaluated for unstable angina had ambulatory electrocardiographic (Holter) recordings analyzed by compact analog technique after they had received medical treatment (3 of the 52 had unanalyzable recordings and were excluded). From 1,103 hours of recordings, 298 ischemic episodes were identified, only 9% associated with angina. By Ridit analysis a significant correlation was found between the cumulative duration of transient myocardial ischemia and the number of diseased coronary vessels and indexes of proximal stenosis. During a 3 to 6 month follow-up period, there was one death and one patient was lost to follow-up among 20 patients without transient ischemia; in the group of 11 patients with a cumulative duration of transient ischemia less than 60 minutes/24 h, 7 were alive and well, 2 required coronary bypass surgery, 1 had coronary angioplasty for recurrence of angina and 1 was lost to follow-up. In the group of 18 patients with ischemia duration greater than 60 minutes/24 h, only 1 developed a stable angina pattern; 12 required coronary surgery (n = 11) or angioplasty (n = 1) and 5 developed myocardial infarction (2 died, 2 needed surgery for postinfarction angina and 1 recovered). A favorable clinical outcome occurred in only 6% of patients in the group with ischemia duration greater than 60 minutes/24 h; this rate was significantly lower (p less than 0.001) than that (70%) for the group with ischemia duration less than 60 minutes/24 h or that (95%) for the group without ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial Ischemia during Cocaine Withdrawal

STUDY OBJECTIVE To determine the prevalence of myocardial ischemia in patients with cocaine addiction. DESIGN Myocardial ischemia in chronic cocaine users was detected by serial 24-hour electrocardiographic ambulatory (Holter) monitoring and exercise treadmill testing in chronic cocaine users. The Holter tapes were coded, scanned in a blinded manner, and mixed with the tapes of 42 normal volunteers and 119 patients with either stable or unstable angina. SETTING A 28-day inpatient, substance abuse treatment program followed by an outpatient treatment program. PATIENTS Twenty-one consecutive male chronic cocaine users. MAIN RESULTS Eight of the 21 patients with cocaine addiction had frequent episodes of ST elevation during Holter monitoring; these episodes occurred almost exclusively during the first 2 weeks of withdrawal. None of the volunteers and patients with stable angina and only 4% of the patients with unstable angina had episodes of ST elevation during Holter monitoring (cocaine users compared with volunteers, P = 0.0004). Of the 20 cocaine patients who had exercise treadmill testing, only 1 had a positive test for ischemia. CONCLUSIONS Cocaine users frequently develop silent myocardial ischemia manifesting as episodes of ST elevation during the first weeks of withdrawal. The underlying mechanisms for these changes remain unknown, but our observations support the hypothesis that coronary vasospasm plays an important role in cocaine-related ischemic syndromes.

Differentiating cardiomyopathy of coronary artery disease from nonischemic dilated cardiomyopathy utilizing positron emission tomography

To determine if imaging of blood flow (using N-13 ammonia) and glucose metabolism (using F-18 2-deoxyglucose) with positron emission tomography can distinguish cardiomyopathy of coronary artery disease from nonischemic dilated cardiomyopathy, 21 patients with severe left ventricular dysfunction who were evaluated for cardiac transplantation were studied. The origin of left ventricular dysfunction had been previously determined by coronary angiography to be ischemic (11 patients) or nonischemic (10 patients). Images were visually analyzed by three observers on a graded scale in seven left ventricular segments and revealed fewer defects in dilated cardiomyopathy compared with ischemic cardiomyopathy for N-13 ammonia (2.7 +/- 1.6 versus 5 +/- 0.6; p less than 0.03) and F-18 deoxyglucose (2.8 +/- 2.1 versus 4.6 +/- 1.1; p less than 0.03). An index incorporating extent and severity of defects revealed more homogeneity with fewer and less severe defects in subjects with nonischemic than in those with ischemic cardiomyopathy as assessed by imaging of flow (2.8 +/- 1.8 versus 9.2 +/- 3; p less than 0.001) and metabolism (3.8 +/- 3.3 versus 8.5 +/- 3.6; p less than 0.005). Diagnostic accuracy for distinguishing the two subgroups by visual image analysis was 85%. Using previously published circumferential count profile criteria, patients with dilated cardiomyopathy had fewer ischemic segments (0.4 +/- 0.8 versus 2.5 +/- 2 per patient; p less than 0.01) and infarcted segments (0.1 +/- 0.3 versus 2.4 +/- 1.4 per patient; p less than 0.001) than did patients with cardiomyopathy of coronary artery disease. The sensitivity for differentiating the two clinical subgroups using circumferential profile analysis was 100% and the specificity 80%. An index incorporating both number and severity of defects derived from circumferential profile analysis was significantly lower in subjects with dilated cardiomyopathy than in ischemic cardiomyopathy (0.3 +/- 0.8 versus 2.7 +/- 2.4; p less than 0.005). Thus, noninvasive positron emission tomographic imaging with N-13 ammonia and F-18 deoxyglucose is helpful in distinguishing patients with severe left ventricular dysfunction secondary to coronary artery disease from those with nonischemic cardiomyopathy, and a semiquantitative index such as circumferential profile analysis is superior to that of visual analysis alone.

Positron emission tomography detects metabolic viability in myocardium with persistent 24-hour single-photon emission computed tomography 201Tl defects.

BACKGROUND Four-hour 201Tl redistribution images underestimate myocardial viability in patients with coronary artery disease (CAD). Because 4-hour defects often redistribute late, delayed imaging may enhance assessment of tissue viability. Myocardial metabolic activity was therefore assessed with positron emission tomography (PET) in 26 CAD patients with impaired ventricular function (ejection fraction, 32.1 +/- 13.9%) and 24-hour single-photon emission computed tomography (SPECT) 201Tl defects. METHODS AND RESULTS On circumferential profile analysis, PET ischemia was defined by preserved glucose metabolism in hypoperfused myocardium, and PET infarction was defined by concordant reductions in perfusion and metabolism. On 19 stress-redistribution and seven rest-redistribution SPECT studies, four observers visually scored 201Tl activity in eight segments on a scale from 0 (normal) to 3 (complete defect). Using an improvement in visual score > or = 0.75 to define redistribution, there were 100 fixed, 17 partially reversible, and 12 completely reversible defects. PET identified tissue metabolic activity in 51 (51%) segments with fixed defects (21 PET ischemia, 30 PET normal) and nine (53%) segments with partially reversible defects (five PET ischemia, four PET normal). When grouped by 24-hour score, the proportion of fixed defects with metabolic activity varied from 84% (scores < or = 1.4) to 15% (scores > 2.6). For partially reversible defects, only 53% with scores < 2.0 and one of two with scores > or = 2.0 were considered metabolically viable on PET. Of 12 completely reversible defects, six (50%) were normal, five (42%) had PET ischemia, and one (8%) had PET infarction. The proportion of fixed defects with metabolic activity did not depend on whether a rest or stress study was performed or on the change in visual score used to define 201Tl redistribution (0.25, 0.50, 0.75, and 1.00). CONCLUSIONS In CAD patients, PET identifies glucose metabolic activity in the majority of fixed 24-hour 201Tl defects. However, very severe (near-complete) 24-hour 201Tl defects are less likely to exhibit metabolic activity on PET imaging than are defects with less-pronounced reductions in segmental 201Tl activity.

Comparative testing of 5 nicotine systems: initial use and preferences.

OBJECTIVE To test initial reactions to 5 nicotine treatments (NRTs: 2 and 4 mg gum, inhaler, nasal spray, tablet) in a crossover study (n=41). METHODS Subjects used each medication on arising (1/2 day) and resumed smoking each afternoon. Subjects rated (individually) and ranked (comparatively) treatments on use, reinforcement, withdrawal, craving, and preferences. RESULTS Overall preferences: inhaler (49%), 4 mg gum (24%), 2 mg gum (10%), 2 mg tablet (10%), nasal spray (7%). Overall results were consistent with ratings and rankings of individual characteristics of drugs. CONCLUSION Subjects had varied reactions to NRTs that may affect initiation of cessation.

Antiarrhythmic Agents for Atrial Fibrillation: Focus on Prolonging Atrial Repolarization

Atrial fibrillation (AF) has been the subject of considerable attention and intensive clinical research in recent years. Current opinion among physicians on the management of AF favors the restoration and maintenance of normal sinus rhythm. This has several potential benefits, including the alleviation of arrhythmia-associated symptoms, hemodynamic improvements, and possibly a reduced risk of thromboembolic events. After normal sinus rhythm has been restored, antiarrhythmic therapy is necessary to reduce the frequency of AF recurrence. In the selection of an antiarrhythmic agent, both efficacy and safety should be taken into consideration. Many antiarrhythmic agents have the capacity to provoke proarrhythmia, which may result in an increase in mortality. This is of particular concern with sodium-channel blockers in the context of patients with structural heart disease. Flecainide and propafenone are well tolerated and effective in maintaining sinus rhythm in patients without significant cardiac disease but with AF. Recent interest has focused on the use of class III antiarrhythmic agents, such as amiodarone, sotalol, dofetilide (recently approved), ibutilide (approved for chemical conversion of AF and atrial flutter), and azimilide (still to be approved) in patients with AF and structural heart disease. To date, amiodarone and sotalol still hold the greatest interest, and although controlled clinical trials with these agents have been few, a number are in progress and some have been recently completed. These agents are effective in maintaining normal sinus rhythm in patients with paroxysmal and persistent AF and are associated with a low incidence of proarrhythmia when used appropriately. Because of the relative paucity of placebo-controlled trials of antiarrhythmic agents in patients with AF, experience until recently has tended to dictate treatment decisions. Increasingly, selection of drug therapy is being based on a careful and individualized benefit-risk evaluation by means of controlled clinical trials, an approach that is likely to dominate the overall approach to the control of atrial fibrillation in the largest numbers of cases of the arrhythmia. Pharmacologic therapy is likely to be dominated by compounds that exert their predominant effect by prolonging atrial repolarization.

Variability of indexes for myocardial ischemia: A comparison of exercise treadmill test, ambulatory electrocardiographic monitoring and symptoms of myocardial ischemia

Fifty-four patients with chronic stable angina were studied to determine and compare weekly variability of indexes for the detection of myocardial ischemia. All patients underwent three single-blind placebo periods, each lasting 1 week. An exercise treadmill test, 24 h ambulatory electrocardiographic (Holter) monitoring (analyzed blindly) and an accurate diary of anginal attacks and nitroglycerin use were obtained at the end of each placebo period. An unbalanced, completely random component of variance analysis was used to calculate a component for within subject variability and a component for among subject variability. The coefficient of variation and percent variation (within subjects) of onset of chest pain during exercise were 19% and 30%, respectively; the corresponding values were 28% and 33% for onset of 1 mm ST depression, 15% and 15% for exercise duration, 44% and 27% for number of ischemic episodes/24 h, 56% and 43% for anginal frequency and 55% and 27% for nitroglycerin consumption, respectively. With use of this statistical method and variation within subjects, the change in the value of each variable necessary to exceed those attributable to spontaneous variation was determined. The trade-off between repeated measurements and number of subjects, the sample size estimated for planning studies and the minimal sample size for using various designs were also determined. Although the data indicate that all indexes for myocardial ischemia, both during exercise and during daily activity, vary considerably, but the exercise variables have less variability and are more reproducible.(ABSTRACT TRUNCATED AT 250 WORDS)

Impact of a Multidisciplinary Heart Failure Post-hospitalization Program on Heart Failure Readmission Rates

Background: Specialized chronic heart failure (HF) clinics have demonstrated significant reductions in readmissions. Limited evidence is available regarding HF clinics in the immediate post-discharge period. Objective: To evaluate the effect of a multidisciplinary HF clinic on 90-day readmission rates and all-cause mortality in those recently discharged from a HF hospitalization. Methods: In this retrospective cohort study, patients discharged with a primary HF diagnosis who attended the HF postdischarge clinic in 2010-2012 were compared with controls from 2009. During 6 clinic visits, patients were seen by a physician assistant, clinical pharmacist specialist, and case manager, with care overseen by a cardiologist. The program focused on optimizing therapy, identifying HF etiology/precipitating factors, medication titration, education, and medication adherence. The primary outcome was 90-day HF readmission. A multivariate Cox proportional hazards model was used to compare outcomes. Results: Among the 277 patients (144 clinic, 133 control) in the study, 7.6% of patients in the clinic and 23.3% of patients in the control group were readmitted for HF within 90 days (aHR (adjusted hazard ratio) = 0.17; 95% CI = 0.07-0.41; P < 0.001; ARR (absolute risk reduction) = 15.7%; NNT (number needed to treat) = 7). Clinic patients had lower 90-day time-to-first HF readmission or all-cause mortality (9.0% vs 28.6%; aHR = 0.28; 95% CI = 0.06-0.31; P < 0.001; ARR = 19.6%; NNT = 6). Conclusions: The multidisciplinary HF posthospitalization outpatient program was associated with a significant reduction in 90-day HF readmissions in patients who were recently discharged from a HF hospitalization.

Stretchable electrochemical impedance sensors for intravascular detection of lipid-rich lesions in New Zealand White rabbits

Flexible electronics have enabled catheter-based intravascular sensing. However, real-time interrogation of unstable plaque remains an unmet clinical challenge. Here, we demonstrate the feasibility of stretchable electrochemical impedance spectroscopy (EIS) sensors for endoluminal investigations in New Zealand White (NZW) rabbits on diet-induced hyperlipidemia. A parylene C (PAC)-based EIS sensor mounted on the surface of an inflatable silicone balloon affixed to the tip of an interrogating catheter was deployed (1) on the explants of NZW rabbit aorta for detection of lipid-rich atherosclerotic lesions, and (2) on live animals for demonstration of balloon inflation and EIS measurements. An input peak-to-peak AC voltage of 10 mV and sweeping-frequency from 300 kHz to 100 Hz were delivered to the endoluminal sites. Balloon inflation allowed EIS sensors to be in contact with endoluminal surface. In the oxidized low-density-lipoprotein (oxLDL)-rich lesions from explants of fat-fed rabbits, impedance magnitude increased significantly by 1.5-fold across the entire frequency band, and phase shifted ~5° at frequencies below 10 kHz. In the lesion-free sites of the normal diet-fed rabbits, impedance magnitude increased by 1.2-fold and phase shifted ~5° at frequencies above 30 kHz. Thus, we demonstrate the feasibility of stretchable intravascular EIS sensors for identification of lipid rich lesions, with a translational implication for detecting unstable lesions.

Rates and predictors of ACE inhibitor discontinuation subsequent to elevated serum creatinine: a retrospective cohort study

Objectives ACE inhibitors (ACEI) are underutilised despite cardiovascular benefits, in part due to concerns of known transient elevations in serum creatinine (SCr) after initiation. Our objectives were to evaluate rates and predictors of ACEI discontinuation after SCr elevation post-ACEI initiation since limited data are available that examine this issue. Setting Primary and tertiary Veterans healthcare system in Los Angeles, California, USA Participants 3039 outpatients initiating an ACEI with a SCr measured within 6 months prior to and approximately 3 months after initiating an ACEI. Patients were divided into three groups (SCr <1.5, 1.5–2 and >2). Primary and secondary outcome measures Rates and factors associated with ACEI discontinuation subsequent to SCr elevation after ACEI initiation and for patients with baseline SCr >2 mg/dL, the change in SCr associated with chronic use. Predictors were identified using multivariate logistic regression modelling. Results At 3 months follow-up, for those with an increase in SCr, the mean increase post-ACEI initiation was 26%, ranging from −0.01 mg/dL to 0.42 mg/dL varying according to a level of baseline renal function. ACEI discontinuation was higher in patients with elevated baseline SCr (19/165, 11.5%) compared with those with SCr <1.5 (135/2497, 5.4%), and those with SCr 1.5–2.0 (28/377, 7.4%). Male patients, and those with heart failure were less likely to discontinue ACEI after an elevation of SCr post-ACEI initiation, while those taking non-steroidal anti-inflammatory drugs, diuretics and β-blockers were more likely to discontinue ACEI. Conclusions SCr increases <30% on average within 3 months of ACEI initiation, with subsequent discontinuation rates varying by baseline SCr. Elevation in SCr was not associated with ACEI discontinuation rates. In patients with SCr >2 mg/dL at baseline, despite an acute increase in SCr after ACEI initiation, chronic ACEI use was associated with a decrease in SCr in most patients.