S. Sultan Ahmed

Evidence for Cardiomyopathy in Familial Diabetes Mellitus

Recent epidemiologic studies have suggested that cardiac disease in common in diabetics and may often have a noncoronary basis. To examine the status of the left ventricle, 17 adult-onset diabetics of familial type without hypertension or obesity underwent hemodynamic study and were compared to 9 controls of similar age. Of the 17, 12 subjects had no significant occlusive lesions by coronary angiography. From this group eight without heart failure had a modest, but significant, elevation of left ventricular end-diastolic pressure. End-diastolic and stroke volumes were reduced, but ejection fraction and mean rate of fiber shortening were within normal limits. The left ventricular end-diastolic pressure/volume ratio was significantly higher than controls. Afterload increments effected a significant increase of filling pressure compared to normals without a stroke volume response, consistent with a preclinical cardiomyopathy. Four patients with prior heart failure had similar but more extensive abnormalities. None had local dyskinesia by angiography, and lactate production was not observed during pacing-induced tachycardia. Left ventricular biopsy in two patients without ventricular decompensation showed interstitial collagen deposition with relatively normal muscle cells. These findings suggest a myopathic process without ischemia. Postmortem studies were performed in 11 uncomplicated diabetics. Nine were without significant obstructive disease of the proximal coronary arteries, and the majority succumbed with cardiac failure. On left ventricular sections, none had evident luminal narrowing of the intramural vessels. All nine exhibited periodic acid-Schiff-positive material in the interstitium. Collagen accumulation was present in perivascular loci, between myofibers, or as replacement fibrosis. Multiple samples of left ventricle and septum revealed enhanced triglyceride and cholesterol concentrations, as compared to controls. Thus, a diffuse extravascular abnormality may be a basis for cardiomyopathic features in diabetes.

Preclinical cardiomyopathy in chronic alcoholics: A sex difference

Alcoholic subjects differ in the incidence of cardiomyopathy. Of potential variables, sex may be important since few females are seen with cardiomyopathy, even adjusting for the lower incidence of alcoholism. To examine this question, noninvasive systolic time intervals were measured in 22 males and 14 females of similar age, heart rate, and arterial pressure, without clinical evidence of heart disease or hypertrophy. Duration and intensity of ethanol intake and the interval from last drinking episode were apparently equivalent. In male alcoholics, the left ventricular preejection period and ejection time (PEP/LVET) ratio of 0.410 +/- 0.020 was significantly higher than in the 11 normal males (0.316 +/- 0.007) (P less than 0.001). In female alcoholics, the ratio was 0.322 +/- 0.015, compared to 0.310 +/- 0.01 for 11 normal females, and was significantly less than in the male patients (P +/- 0.001). In addition prolonged intraventricular conduction by high-frequency ECG was more prevalent in the male group. To further ensure equivalency of alcoholism, patients with biopsy-proved cirrhosis were selected. In nine males, PEP/LVET was significantly higher than in the 10 females. Thus, abnormal myocardial function was evident in males but not in females, suggesting that sex is a determinant of the toxic effects of ethanol on myocardium.

The STAT-MI (ST-Segment Analysis Using Wireless Technology in Acute Myocardial Infarction) Trial Improves Outcomes

OBJECTIVES The goal of this study was to evaluate the impact of the STAT-MI (ST-Segment Analysis Using Wireless Technology in Acute Myocardial Infarction) network on outcomes in the treatment of patients presenting with ST-segment elevation myocardial infarction (STEMI). BACKGROUND Shortening door-to-balloon (D2B) time remains a national priority for the treatment of STEMI. We previously reported a fully automated wireless network (STAT-MI) for transmission of electrocardiograms (ECGs) for suspected STEMI from the field to offsite cardiologists, allowing early triage with shortening of subsequent D2B times. We now report the impact of the STAT-MI wireless network on infarct size, length of hospital stay (LOS), and mortality. METHODS A fully automated wireless network (STAT-MI) was developed to enable automatic 12-lead ECG transmission and direct communication between emergency medical services personnel and offsite cardiologists that facilitated direct triage of patients to the cardiac catheterization laboratory. Demographic, laboratory, and time interval data of STAT-MI network patients were prospectively collected over a 33-month period and compared with concurrent control patients who presented with STEMI through non-STAT-MI pathways. RESULTS From June 2006 through February 2009, 92 patients presented via the STAT-MI network, and 50 patients presented through non-STAT-MI pathways (control group). Baseline clinical and demographic variables were similar in both groups. Overall, compared with control subjects, STAT-MI patients had significantly shorter D2B times (63 [42 to 87] min vs. 119 [96 to 178] min, U = 779.5, p < 0.00004), significantly lower peak troponin I (39.5 [11 to 120.5] ng/ml vs. 87.6 [38.4 to 227] ng/ml, U = 889.5, p = 0.005) and creatine phosphokinase-MB (126.1 [37.2 to 280.5] ng/ml vs. 290.3 [102.4 to 484] ng/ml, U = 883, p = 0.001), higher left ventricular ejection fractions (50% [35 to 55] vs. 35% [25 to 52], U = 1,075, p = 0.004), and shorter LOS (3 [2 to 4] days vs. 5.5 [3.5 to 10.5] days, U = 378, p < 0.001). CONCLUSIONS A fully automated, field-based, wireless network that transmits ECGs automatically to offsite cardiologists for the early evaluation and triage of patients with STEMI shortens D2B times, reduces infarct size, limits ejection fraction reduction, and shortens LOS.

Cardiac function in alcoholics with cirrhosis: Absence of overt cardiomyopathy—myth or fact?

Cardiomyopathy in alcoholics is considered to be associated with a low incidence of hepatic cirrhosis. To evaluate cardiac hemodynamics in alcoholic liver disease, left ventricular function in 37 patients with hepatic cirrhosis (group II) was compared with that in 13 normal subjects (group I) matched for age, sex and cardiac size. These groups were contrasted with group III, comprising 32 alcoholics without cirrhosis who had cardiac symptoms but no cardiomegaly or heart failure. Patients with cirrhosis as a group did not differ from normal subjects (group I) in terms of left ventricular filling pressure and cardiac muscle and pump function (cardiac index). However, subgroup IIA (n = 21) had a stroke index significantly less than normal, while subgroup IIB had a significantly increased stroke index and myocardial cardial contractility with a diminished systemic arterial resistance. Similar hepatic abnormalities were present in both subgroups. In group III, left ventricular end-diastolic and aortic mean pressures were significantly elevated compared with values in normal subjects, while cardiac index and indexes of ventricular contraction and relaxation were abnormal. Further examination of patients with cirrhosis indicated that the responses to volume or pressure increments in terms of the level of stroke work for a given filling pressure were most abnormal in group IIA, approximating those of group III. Thus, although overt cardiomyopathy is infrequent in patients with cirrhosis, asymptomatic myocardial disease may assume clinical importance during volume or pressure overload.

Sustained effect of glucose-insulin-potassium on myocardial performance during regional ischemia. Role of free fatty acid and osmolality.

To evaluate the influence of glucose infusate administered with insulin and potassium on left ventricular function during 4 h of ischemia, as well as mechanism of action, four groups of intact anesthetized dogs were studied. Acute regional ischemia was induced with a balloon tip catheter in the left anterior descending artery and infusates were begun after 20 min of ischemia. A threefold increase of plasma glucose concentration was associated with improved left ventricular function during ischemia, compared to animals receiving isovolumic saline. There was a significant decline of left ventricular end-diastolic pressure associated with elevation of stroke volume and ejection fraction to control levels, as determined by indicator dilution. In a separate subgroup studied by cineangiography, shortening of the ischemic anterior wall, after an initial decline, was increased in response to glucose but there was no evidence of extension of injury. Ischemic tissue exhibited a smaller gain of water as well as Na+ per gram dry weight as compared to ischemic controls. On precordial electrocardiogram mapping there was a significant decrease in the sigmaST (sum of ST elevation) as well as NST (number of ST segment elevations), but the reduction of R wave amplitude was not different from controls. To further evaluate long-term effects, eight controls and six treated animals underwent myocardial ischemia and were sacrificed after 4 mo. Calculated area and weight of scar, as well as degree of wall thinning, were similar in both groups. The glucose-treated animals had a significant decrease of plasma FFA in contrast to controls which manifested a significant rise. To examine the postulate that the decrease in FFA was important to therapeutic action, a third group was infused with Intralipid (Cutter Laboratories, Inc., Berkeley, Calif.) and heparin, simultaneously with the glucose infusate, to effect an elevation of plasma FFA during ischemia. Changes in myocardial function and electrolyte composition, as well as precordial electrocardiogram mapping, were similar to that of animals receiving glucose alone. Because serum osmolality was increased approximately 40 mosmol during the glucose infusion, the potential role of hyperosmolality was assessed by infusion of 20% mannitol during acute ischemia in a fourth group. After a transient small increase, there was a moderate decline in function by 4 h, suggesting that the response to glucose is not dependent upon extracellular osmolality. Thus, it is concluded that during the initial hours after the onset of myocardial ischemia the glucose infusate improves ventricular performance without evidence of arrhythmia induction or intensification of ischemic injury. Evolution of irreversible necrosis appears to be delayed rather than prevented under the circumstances of this study.

The state of the left ventricular myocardium in mitral stenosis

Summary Subnormal stroke volume (SV) and ejection fraction (EF) in mitral stenosis (MS) have been attributed to abnormality in the left ventricular (LV) myocardium despite studies in this laboratory showing normal LV myocardial contractility and oxidative metabolism. To clarify this problem, LV function was studied in 10 patients with pure MS, seven with cardiomyopathy (MYO) who had normal LV preload (end-diastolic volume) and afterload (mean systolic tension), six with atrial septal defect (ASD), and in 10 normal subjects (N). All three patient groups were characterized by subnormal SV, EF, and contractile telement velocity (Vce) at peak dP/dt despite normal preload and afterload. However, the Frank-Levinson contractility index, which normalizes Vce for diastolic fiber length, was depressed only in MYO (0.73±0.07 vs 1.39±0.07 in the N, P

Spontaneous heart rate, ventricular tachycardia, and the response to procainamide during acute ischemia*

Summary Acute pacing-induced tachycardia in early ischemia allegedly promotes ventricular arrhythmias which appear unresponsive to antiarrhythmic agents, rasing question as to the efficacy of drug intervention clinically. To determine whether spontaneous sinus rate has the same relationship to arrhythmia incidence and responsiveness in the intact anesthetized dog, 82 animals were continuously monitored during a high-risk arrhythmic period, the inital 15 minutes of ischemia. Proximal occlusion of the anterior descending artery was induced by inflating a balloon tipped catheter. There was a modest increase in the incidence of VPBs at heart rates of 106 to 140 per minute compared to 70 to 105 beats, which was not seen at higher heart rates. However, ventricular tachycardia was not correlated with the sinus rate over a range of 70 to 210 beats per minute. To assess the relation of heart rate and responsiveness to antiarrhythmic agents, a group of 17 dogs received procainamide, 10 mg./Kg. intravenously at the onset of ventricular tachycardia. These were compared with an untreated group having similar heart rate levels and equivalent injury in terms of the number and sum of precordial leads with ST segment elevation. Nine of the 18 untreated animals with VPBs progressed to fibrillation; the incidence of fibrillation was reduced to one of 17 after procainamide (P