Ralf Polikar

Short- and long-term clinical outcome after Q wave and non-Q wave myocardial infarction in a large patient population.

Prognosis for patients with non-Q wave myocardial infarction is controversial although a number of studies have shown a less favorable outlook after hospital discharge for patients with non-Q wave than for those with Q wave infarction. Therefore, the in-hospital and 1-year prognosis was investigated in a sufficiently large patient population (n = 2,024) to allow stratification by subgroups, in particular by age and previous myocardial infarction. Patients with non-Q wave infarction (n = 444; 22% of the total study population) were somewhat older (65 vs. 63 years, p less than 0.001) and had an increased incidence of previous myocardial infarction (46% vs. 24%, p less than 0.001) and congestive heart failure (21% vs. 8%, p less than 0.001) than patients with Q wave infarction. In-hospital mortality of patients with non-Q wave infarction was lower (8.1% vs. 11.5%; p less than 0.06), whereas their 1-year mortality after hospital discharge was significantly higher (13.7% vs. 9.2%, p less than 0.05) than for patients with Q wave infarction. However, total mortalities at 1 year were nearly equal. When patients were subgrouped by presence or absence of a previous myocardial infarction, patients in both subgroups exhibited mortality patterns typical of the entire population with Q wave or non-Q wave infarction. However, when stratified by age and previous infarction, in-hospital mortality for patients with non-Q wave infarction was significantly lower only in patients older than 70 years of age. Similarly, the higher mortality after hospital discharge in patients with non-Q wave infarction occurred only in patients older than 70 years of age without previous myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Familial aortic dissecting aneurysm.

A family is described in which nine members over two generations had an aortic dissecting aneurysm or aortic or arterial dilation at a young age. The family has been followed up since 1977 after the death of a second teenager from a kindred of 11. None of the patients had the Marfan syndrome or a history of systemic hypertension. Three members died of ruptured aortic dissecting aneurysm and acute hemopericardium at 14, 18 and 24 years of age, respectively; a fourth member died suddenly at age 48 years, a few years after aortic repair for aneurysmal dilation. One member underwent surgical repair of an ascending aortic dissecting aneurysm at age 18 years and is still alive. Four members are currently under close medical observation for aortic or arterial dilation. Histologic examination of the aortic wall at autopsy or surgery in three patients revealed a loss of elastic fibers, deposition of mucopolysaccharide-like material in the media and cystic medial changes. Types I and III collagen from cultured fibroblasts appeared normal on gel electrophoresis. Results of indirect immunofluorescent studies of the elastin-associated microfibrillar fiber array in skin and fibroblast culture from multiple family members were also normal. This dramatic familial cluster of aortic dissecting aneurysm and aortic or arterial dilation suggests a genetically determined disease of autosomal dominant inheritance although the basic defect remains unknown.

Long-Term Outcome in Patients With Inferior Myocardial Infarction and Complete Atrioventricular Block

Some studies have reported increased short-term mortality and higher incidence of multivessel coronary artery disease in patients with inferior myocardial infarction and complete heart block, but information is lacking on clinical outcome after hospital discharge. Therefore, data were obtained and analyzed in 749 patients who were admitted with inferior myocardial infarction to four different centers and followed up for 1 year. Six hundred fifty-four patients (Group 1) did not have complete heart block and 95 (Group 2) had complete heart block during their hospital stay (incidence rate 12.8%). Compared with Group 1, Group 2 patients were older (66 versus 61 years, p less than 0.01), more often had signs of left ventricular failure (p less than 0.001) and had higher peak creatine kinase values (1,840 versus 1,322 IU/liter, p less than 0.001). The in-hospital mortality rate was higher in Group 2 than in Group 1 (24.2 versus 6.3%, p less than 0.001). However, at discharge there was no difference between Group 1 and Group 2 in clinical characteristics, left ventricular ejection fraction (0.52 +/- 0.12 versus 0.52 +/- 0.11) or incidence of complex ventricular arrhythmias on ambulatory electrocardiographic monitoring. Furthermore, during the year after hospital discharge, patients in Groups 1 and 2 did not have significantly different mortality rates (6.4 versus 10.1%, p = NS). The incidence rate of reinfarction (4%) was the same in Groups 1 and 2. The incidence of coronary artery bypass surgery was slightly but not significantly higher in Group 1 compared with Group 2 (11 versus 4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Connexin37 in normal and pathological development of mouse heart and great arteries

Cx37 is a member of the connexin family of gap junction proteins, whose distribution in heart remains controversial. We have generated novel antibodies against Cx37 to investigate this distribution during normal and pathological development in mouse. Using these affinity‐purified antibodies, we have detected Cx37 in hearts and aortas of mouse embryos from day 11 ed. onwards. Immunostaining revealed that during prenatal development Cx37 predominated in endothelial and endocardial cells but was also detectable in small amounts in the trabeculated and compact layers of ventricular myocardium, as well as in the mesenchyme of conotruncal ridges and atrioventricular cushions. Cx37 was also differentially expressed in the ascending and descending portions of the embryonic aorta, according to a pattern which differed in the three layers of the vessel wall. Cx37 distribution was altered in both heart and aorta of mice that had been exposed to all‐trans retinoic acid at the beginning of foetal development, whether or not these animals subsequently developed a transposition of great arteries. The data indicate that Cx37 is widely distributed in multiple compartments of cardiovascular system, in patterns which are modulated during development, by retinoic acid. Dev Dyn;218:331–344.

Decreased adrenergic sensitivity in patients with hypothyroidism

Cardiovascular sensitivity to catecholamines was assessed in 15 patients with hypothyroidism (mean [+/- SEM] thyroxine [T4] index 2.7 +/- 0.5 micrograms/100 ml, thyroid stimulating hormone [TSH] 136.9 +/- 48.3 microU/ml), aged 45 +/- 4 years and in 8 healthy control subjects. The study was repeated in 10 patients with hypothyroidism 4.0 +/- 0.5 months after thyroid replacement therapy (T4 index 9.9 +/- 2.1 micrograms/100 ml, TSH 3.5 +/- 1.3 microU/ml). In addition, basal, average and maximal heart rates were measured using 24 h ambulatory electrocardiographic (ECG) monitoring, and plasma levels of epinephrine and norepinephrine were determined before and after thyroid replacement. Heart rate increased less after bolus injection of 0.8, 1.6 and 3.2 micrograms of isoproterenol in the hypothyroid (10 +/- 2, 15 +/- 2 and 21 +/- 4 beats/min, respectively) than in the euthyroid (16 +/- 3, 22 +/- 3 and 30 +/- 4 beats/min, respectively) state (p less than 0.05). Control subjects reacted similarly to patients receiving thyroid replacement. Basal heart rate (64 +/- 3 versus 68 +/- 3 beats/min, p less than 0.05) and maximal heart rate (116 +/- 5 versus 133 +/- 5 beats/min, p less than 0.05) were lower on 24 h ambulatory ECG monitoring in the hypothyroid than euthyroid state despite higher basal plasma norepinephrine levels (394 +/- 45 versus 315 +/- 45 pg/ml, p less than 0.05). Thus, patients with hypothyroidism display a decreased cardiac chronotropic response to beta-adrenergic stimulation. This may contribute in part to the decreased basal and maximal daily heart rates seen in patients with hypothyroidism, which occurs despite elevated plasma norepinephrine levels.

Effect of thyroid replacement therapy on the frequency of benign atrial and ventricular arrhythmias

Whether thyroid replacement therapy can trigger cardiac arrhythmias in patients with hypothyroidism is not known. In this prospective study, 24 h ambulatory electrocardiographic (ECG) monitoring was used to assess the frequency of atrial and ventricular premature beats in 25 patients with hypothyroidism (5 men and 20 women, aged 56 +/- 3 years) before and 3.5 +/- 0.5 months (mean +/- SEM) after thyroid replacement therapy. Plasma thyroid-stimulating hormone was 73.6 +/- 12.3 and 3.1 +/- 0.6 microU/ml and free thyroxine index was 2.4 +/- 0.4 and 9.8 +/- 0.9 micrograms/100 ml at baseline and after thyroid replacement therapy, respectively. The frequency of ventricular premature beats was not affected by thyroid replacement therapy (from 273 +/- 221 at baseline to 352 +/- 235 beats/24 h after therapy), even in patients with frequent baseline arrhythmias. In contrast, the frequency of atrial premature beats was slightly increased after thyroid replacement therapy (from 47 +/- 17 to 279 +/- 197 beats/24 h), largely as a result of changes seen in three patients. No patient developed new onset of sustained ventricular or supraventricular arrhythmias. Average, basal and maximal heart rates during ECG monitoring increased significantly after thyroid replacement therapy (average 72 +/- 2 to 80 +/- 2; basal 64 +/- 2 to 70 +/- 2; maximal 114 +/- 3 to 130 +/- 3 beats/min, respectively, p less than 0.001). In conclusion, thyroid replacement therapy is safe in patients with common benign cardiac arrhythmias, and does not trigger an increase in arrhythmia frequency except in rare patients with baseline atrial premature beats. It is, however, associated with an increase in basal, average and maximal heart rates.

Effect of oral triiodothyronine during amiodarone treatment for ventricular premature complexes

Whether there is a link between the antiarrhythmic efficacy of amiodarone and its blocking effect on the peripheral conversion of tetraiodothyronine (T4) to triiodothyronine (T3) is uncertain. If such a link exists, oral intake of T3 during amiodarone treatment could reverse, at least partially, the antiarrhythmic efficacy of amiodarone. To assess the safety of oral intake of T3 during amiodarone treatment and gain further insight into the relation between the antiarrhythmic action of amiodarone and its metabolic effect on T4, 7 patients (aged 32 to 62 years) with multiple ventricular premature complexes (VPCs) but no underlying heart disease were studied. Antiarrhythmic treatment was indicated for symptomatic relief only. Each patient underwent a 48-hour ambulatory electrocardiographic recording, electrocardiography and thyroid function tests, including plasma T4, T3, reverse T3 (rT3), free T4, free T3 and thyroid-stimulating hormone without treatment (baseline) after 1 month of amiodarone therapy and after a second month of amiodarone therapy with increasing doses of oral T3 (up to 75 micrograms/day). Treatment with amiodarone resulted in a decrease in plasma T3 and free T3, an increase in plasma rT3, a marked diminution in the frequency of VPCs and a prolongation of the corrected QT interval (QTc). During treatment with amiodarone and T3, plasma T3 and free T3 increased and plasma T4, free T4 and rT3 levels decreased; the frequency of VPCs remained low despite shortening of the QTc to values not different from baseline. Thus, in patients with frequent VPCs and no underlying heart disease, oral intake of T3 during amiodarone treatment is safe and does not abolish the antiarrhythmic efficacy of amiodarone, despite a shortening of the QTc.(ABSTRACT TRUNCATED AT 250 WORDS)

Echocardiographic evidence of pericardial effusion in severe chronic pulmonary hypertension

Abstract We have frequently observed pericardial effusions in patients with severe chronic pulmonary hypertension. In this study, we retrospectively reviewed all echocardiographic data from 66 patients with chronic severe pulmonary hypertension for evidence of pericardial effusion and, if present, whether it was associated with particular hemodynamic characteristics.