Paul Walinsky

Reperfusion arrhythmia: A marker of restoration of antegrade flow during intracoronary thrombolysis for acute myocardial infarction

We studied the effects of coronary recanalization on arrhythmogenesis in patients undergoing intracoronary thrombolysis during the early hours of myocardial infarction. Catheterization, ventriculography, coronary angiography, and intracoronary streptokinase infusion were performed in 22 patients. Twenty-one of 22 had thrombotic total occlusion of the infarct-related transient thrombolysis with reocclusion by the end of the procedure. In 12 of these 17 patients, restoration of antegrade coronary flow was accompanied by transient arrhythmia. In these 12 patients coronary angiography within seconds of onset of arrhythmia showed vessel patency in a previously totally occluded coronary artery. Two additional patients developed arrhythmias during streptokinase infusion but after reperfusion had already been established. Accelerated idioventricular rhythm was most often noted. Sinus bradycardia and atrioventricular block with hypotension occurred during restoration of flow in arteries supplying the inferoposterior left ventricle. These arrhythmias may be useful noninvasive markers of successful reperfusion during thrombolytic therapy in acute myocardial infarction.

Thromboxane release during pacing-induced angina pectoris: possible vasoconstrictor influence on the coronary vasculature.

We developed a radioimmunoassay for plasma thromboxane B, the metabolite of the coronary vasoconstrictor thromboxane A,. To see if thromboxane A, is produced during myocardial ischemia, we used atrial pacing to study 14 patients with greater than 75% occlusive coronary artery disease proved by arteriography. Paired samples were taken from the coronary sinus (CS) and an artery (A) for lactate and thromboxane B, analysis before pacing. During and after pacing at 140 beats/min, sampling was repeated. Before, during, immediately after and 10 minutes after pacing, percent myocardial lactate extractions (A-CS/A × 100) were 29.3 ± 3.7%, −21.1 ± 12.8%, −74.3 ± 20.3% and 25.1 + 3.5%, respectively (all changes p < 0.01). Before pacing, five patients had detectable coronary sinus or arterial thromboxane levels. During pacing, 18% and 40% increases occurred in coronary sinus and arterial blood, respectively (0.8 ± 0.1 to 0.9 ± 0.2 pmol/ml, and 0.5 0.2 to 0.7 ± 0.2 pmol/ml). Immediately after pacing, increases of 204% and 132% occurred in the coronary sinus and arterial blood (p < 0.05), respectively (2.3 ± 0.9 pmol/ml and 1.2 ± 0.4 pmol/ml). Ten minutes after pacing, thromboxane B, returned to prepacing levels. These data indicate that thromboxane A, is produced during pacing-induced myocardial ischemia and could alter regional coronary blood flow.

Spectrum of coronary arterial spasm. Clinical, angiographic and myocardial metabolic experience in 29 cases

A relationship of coronary arterial spasm to variant angina pectoris, subendocardial ischemia, major ventricular arrhythmias and myocardial infarction has been demonstrated. In 29 patients, spasm was angiographically observed in normal-appearing coronary arteries (7 patients) as well as superimposed on various degrees of coronary atherosclerotic obstruction (22 patients). All patients experienced an atypical anginal syndrome;16 patients also experienced typical exertional angina. Coronary spasm appeared to be a major contributory factor in eight occurrences of myocardial infarction and in 11 incidents of ventricular tachycardia, ventricular fibrillation and heart block. Coronary spasm in the 29 cases was distributed in the following fashion: left main trunk, 6 cases; right main trunk, 12 cases; proximal left anterior descending artery, 13 cases; proximal circumflex artery, 1 case; distal left anterior descending artery, 1 case; and distal circumflex artery, 2 cases. In 5 cases coronary spasm was noted at multiple sites.

Detection of thromboxane B2 in peripheral blood of patients with Prinzmetal's angina

The plasma levels of thromboxane B2 (TxB2) were determined by radioimmunoassay in 6 consecutive patients with Prinzmetals angina and in 9 healthy volunteers. In the normal group TxB2 was not detectable (= 0.5 pmoles/ml), while in patients with variant angina TxB2 was consistently detected (1.5-140 pmole/ml).

Thromboxane A2 in acute myocardial infarction

We evaluated the presence of thromboxane B2, the stable metabolite of thromboxane A2, early in the course of acute myocardial infarction (AMI) in both animal and patient studies. In an open-chest model, the left anterior descending artery (LAD) was isolated and the great cardiac vein was cannulated in nine dogs. Following occlusion of the LAD, there was an increase in thromboxane B2 concentration from 0.77 +/- 0.0093 to 1.79 +/- 0.46 pmol/ml (p less than 0.05) and 1.96 +/- 0.48 pmol/ml (p less than 0.05) at 1 and 5 minutes, respectively, following coronary occlusion. At 30 and 60 minutes after occlusion there was no significant increase compared to the baseline. In 17 patients with AMI the mean thromboxane B2 concentration was 0.96 +/- 0.13 pmol/ml at 4.88 +/- 0.40 hours after the onset of chest pain. In 12 patients with sequential samples before and after restoration of patency of the occluded vessel, the initial concentration was 0.71 +/- 0.058 pmol/ml. At 5 minutes after restoration of patency thromboxane B2 concentration was 1.1 +/- 0.17 pmol/ml (p = 0.05). One hour later a return to baseline was noted (0.82 +/- 0.75 pmol/ml). Two patients with the highest thromboxane B2 concentrations (2.0 and 2.6 pmol/ml) were unable to have successful recanalization. We conclude that generation of thromboxane A2 occurs during the early stages of AMI and may be an important pathophysiologic phenomenon in AMI.

Accuracy of MDCT in Assessing the Degree of Stenosis Caused by Calcified Coronary Artery Plaques

OBJECTIVE Because of beam-hardening and blooming artifacts, it is difficult to determine the degree of stenosis caused by calcified coronary artery plaques at coronary CT angiography (CTA). Our goal was to determine how accurate coronary CTA is in evaluating these lesions. MATERIALS AND METHODS Thirty-one patients who had one or more calcified coronary artery plaques at coronary CTA underwent invasive coronary angiography. The size of the calcified coronary artery plaques was graded subjectively as small, moderate, or large. Using postprocessing techniques such as segmentation and tracking, we attempted to determine whether the calcified lesions were obstructive (> or = 50% diameter narrowing) or nonobstructive (< 50% diameter narrowing). Concordance with invasive coronary angiography was then determined. RESULTS Calcified coronary artery plaques were graded by coronary CTA as small at 61 locations, moderate at 22 locations, and large at 43 locations. Of the 61 small calcified coronary artery plaques, 5% were obstructive at invasive coronary angiography; of the 22 moderate-sized calcified coronary artery plaques, 14% were obstructive; and of the 43 large calcified coronary artery plaques, 42% were obstructive. Concordance between coronary CTA and invasive coronary angiography occurred in 58 of 61 (95%) small calcified coronary artery plaques, 20 of 22 (91%) moderate-sized coronary artery plaques, and 29 of 43 (67%) large coronary artery plaques. Coronary CTA underestimated the degree of stenosis in one small calcified coronary artery plaque but overestimated the degree of stenosis in two small, two moderate, and 14 large coronary artery plaques. In detecting obstructive lesions caused by the 43 large calcified coronary artery plaques, coronary CTA had a sensitivity of 100%, specificity of 44%, positive predictive value of 56%, negative predictive value of 100%, and accuracy of 67%. CONCLUSION Coronary CTA can be used to accurately predict the presence of obstructive disease in > 90% of small and moderate-sized calcified coronary artery plaques. With large calcified coronary artery plaques, CTA correctly predicts the presence of obstructive disease in approximately two thirds of the cases. When errors occur, they are usually due to overestimation of the degree of stenosis.

Efficacy of intracoronary nicardipine in the treatment of no-reflow during percutaneous coronary intervention

Objectives: The goal of this study was to evaluate the safety and efficacy of nicardipine in reversing no‐reflow during percutaneous coronary intervention (PCI). Background: No‐reflow is a common complication of PCI in patients with acute coronary syndromes or venous bypass graft disease. Although nicardipine has an attractive pharmacological profile and has been used clinically to treat no‐reflow, there is a paucity of published data regarding its effectiveness in this setting. Methods: We conducted a retrospective analysis of 72 consecutive patients who received intracoronary nicardipine to reverse no‐reflow during coronary intervention. Qualitative TIMI flow grade and quantitative TIMI frame count methods were used to assess the efficacy of nicardipine. Results: A mean of 460 ± 360 mcg of intracoronary nicardipine was used. No‐reflow was successfully reversed with complete restoration of TIMI 3 flow in 71 of 72 patients (98.6%). TIMI flow grade improved from 1.65 ± 0.53 prior to nicardipine to 2.97 ± 0.24 after treatment (P < 0.001). TIMI frame count decreased from 57 ± 40 at the time of no‐reflow to 15 ± 12 after nicardipine administration (P < 0.001). Nicardipine therapy was well tolerated without adverse hemodynamic or chronotropic effects.Conclusions: In this largest series to date, intracoronary nicardipine was demonstrated to be a safe and highly effective pharmacological agent to reverse no‐reflow during PCI.

Comparison of coronary angiographic findings during the first six hours of non-Q-wave and Q-wave myocardial infarction.

The angiographic features of non-Q-wave acute myocardial infarction (AMI) soon after symptom onset have not been previously reported. Accordingly, this study reviewed the coronary angiographic findings of 86 patients with AMI studied within 6 hours of symptom onset: 58 had Q-wave and 28 had non-Q-wave AMI. Patients with Q-wave and non-Q-wave AMI were comparable in terms of clinical characteristics, frequency of 1-vessel disease, and infarct-related artery location. Thrombus was observed in 49 patients (84%) with Q-wave AMI versus 12 (43%) with non-Q-wave AMI (p = 0.0002). Whereas complete occlusion of the infarct-related artery was present in 53 patients (91%) with Q-wave AMI, total coronary occlusion was present in only 11 (39%) with non-Q-wave AMI (p = 0.0001). Collaterals to occluded infarct arteries were seen in 10 patients (19%) with Q-wave AMI versus 5 (45%) with non-Q-wave AMI (p = 0.06). Residual perfusion of the infarct artery by either anterograde or collateral flow was typical of patients with non-Q-wave AMI (22 of 28, 79%) but was uncommon in those with Q-wave AMI (15 of 58, 26%) (p = 0.0001). Thus, coronary angiography performed within 6 hours of symptom onset demonstrates important differences between Q-wave and non-Q-wave AMI. Non-Q-wave AMI is characterized by partial perfusion of the infarct-related artery by either anterograde or collateral flow, and a lower incidence of thrombus than Q-wave AMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Decreased Levels of BAG3 in a Family With a Rare Variant and in Idiopathic Dilated Cardiomyopathy

The most common cause of dilated cardiomyopathy and heart failure (HF) is ischemic heart disease; however, in a third of all patients the cause remains undefined and patients are diagnosed as having idiopathic dilated cardiomyopathy (IDC). Recent studies suggest that many patients with IDC have a family history of HF and rare genetic variants in over 35 genes have been shown to be causative of disease. We employed whole‐exome sequencing to identify the causative variant in a large family with autosomal dominant transmission of dilated cardiomyopathy. Sequencing and subsequent informatics revealed a novel 10‐nucleotide deletion in the BCL2‐associated athanogene 3 (BAG3) gene (Ch10:del 121436332_12143641: del. 1266_1275 [NM 004281]) that segregated with all affected individuals. The deletion predicted a shift in the reading frame with the resultant deletion of 135 amino acids from the C‐terminal end of the protein. Consistent with genetic variants in genes encoding other sarcomeric proteins there was a considerable amount of genetic heterogeneity in the affected family members. Interestingly, we also found that the levels of BAG3 protein were significantly reduced in the hearts from unrelated patients with end‐stage HF undergoing cardiac transplantation when compared with non‐failing controls. Diminished levels of BAG3 protein may be associated with both familial and non‐familial forms of dilated cardiomyopathy. J. Cell. Physiol. 229: 1697–1702, 2014.

Modulation of hemodynamic effects with a converting enzyme inhibitor: Acute hemodynamic dose-response relationship of a new angiotensin converting enzyme inhibitor, lisinopril, with observations on long-term clinical, functional, and biochemical responses

The hemodynamic effects of varying oral doses of the long-acting converting enzyme inhibitor lisinopril were studied in an acute, single-blind, parallel fashion in 55 patients with moderate to severe congestive heart failure. Doses of 2.5, 5.0, and 10 mg produced a significant increase in cardiac index and significant reductions in pulmonary capillary wedge, right atrial, pulmonary arterial, and systemic arterial pressures and systemic vascular resistance. The changes were present up to 24 hours after dosing for most parameters. There was a clear-cut dose-response relationship observed. Forty-seven patients were followed over a 3-month period, during which functional status and exercise tolerance improved. Although 26% showed some evidence of renal dysfunction with lisinopril, these changes could be normalized by decreasing either the lisinopril or the diuretic dose. These data demonstrate that the hemodynamic changes with the long-acting converting enzyme inhibitor lisinopril can be modulated with dose adjustment in patients with congestive heart failure. They also suggest that renal function changes may be normalized by adjustment of either the dose of lisinopril or the diuretic dose.