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Background Free fatty acids (FFAs) are essential cell nutrients but also important signaling molecules regulating various cellular processes. Short-chain fatty acids (SCFAs), like propionate and butyrate, activate two different types of G protein-coupled receptors (GPCRs), FFAR2 and FFAR3. FFAR3 (also known as GPR41) couples to Gi/o proteins lowering cyclic 3', 5'-adenosine monophosphate (cAMP) levels and activating mitogen-activated protein kinases (MAPKs). In addition to adipose tissue, FFAR3 is highly expressed in peripheral sympathetic ganglia augmenting sympathetic nervous system (SNS) outflow. Regulator of G protein Signaling (RGS)-4 belongs to the RGS superfamily of proteins and inactivates (terminates) both Gi/o- and Gq-protein signaling. Cardiac RGS4 has been implicated in atrial fibrillation (AFib) prevention via calcium signaling attenuation. Finally, β-adrenergic receptors (ARs), the major mediators of catecholaminergic and SNS actions in cardiac myocytes, stimulate cAMP synthesis and activate protein kinase A (PKA), which is known to activate RGS4 via phosphorylation. Objective We examined whether RGS4 regulates cardiac FFAR3 signaling. Methods We used H9c2 cardiomyocytes transfected to express the human FFAR3. After treatment with catecholaminergic agonists and/or propionic acid plus various pharmacological inhibitors and siRNA to deplete RGS4, we performed signaling assays (western blotting, cAMP accumulation, GTP binding, ELISA) to delineate the precise involvement of RGS4 in the cardiac βAR-FFAR3 signaling crosstalk. Results RGS4 is essential for the dampening of propionate/FFAR3-dependent signaling in H9c2 cardiomyocytes since siRNA-mediated RGS4 depletion significantly enhances the effect of propionic acid on cAMP lowering, Gi/o activation, and p38 MAPK activation. Notably, concomitant isoproterenol or salbutamol treatment blocks propionic acid-induced signaling via the FFAR3 in H9c2 cardiomyocytes, indicating negative regulation of FFAR3 by catecholamines via the β2AR. Mechanistically, this is mediated by RGS4, since neither isoproterenol, nor salbutamol can inhibit propionate signaling upon siRNA-mediated RGS4 depletion. Finally, β2AR inhibition of FFAR3 signaling via RGS4 is dependent on β2AR-activated PKA, because pre-treatment with the PKA inhibitor H89 abrogates the catecholaminergic inhibition of FFAR3 signaling in H9c2 cardiomyocytes, as measured by cAMP lowering, downstream p38 MAPK activation, and interleukin (IL)-6 production. Conclusion Catecholamine-activated RGS4 abrogates SCFA/FFAR3 signaling and function in cardiac myocytes. This may represent part of the mechanism via which RGS4 protects against both AFib pathogenesis and FFAR3-promoted SNS hyperactivity and inflammation in the myocardium. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Background We hypothesized that multiple cardiovascular comorbidities, incorporated in the CHA 2 DS 2‐VASc score, may be useful in the assessment of ventricular tachyarrhythmias (VTAs) and mortality risk in heart failure (HF) patients. Methods and Results We evaluated the association between the CHA 2 DS 2‐VASc score (dichotomized as high at the upper quartile [≥5] and further assessed as a continuous measure) and the risk of VTA and death among 1804 patients enrolled in MADIT‐CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy). A high CHA 2 DS 2‐VASc score (n=464; 26%) was inversely associated with the risk of any VTA (hazard ratio [HR]: 0.64; P=0.001), fast VTA >200 beats/min (HR; 0.51; P

This study sought to characterize the presentations, electrophysiological features and diagnostic maneuvers for a series of unique arrhythmias involving the HPS.By virtue of its unique anatomy and ion channel composition, the His-Purkinje system (HPS) is prone to a variety of arrhythmic perturbations.The authors present a collaborative multicenter case series of 6 patients with HPS-related arrhythmias. All patients underwent electrophysiological studies using standard multipolar catheters.In 3 patients, both typical and reverse bundle branch re-entry were seen, with 1 patient demonstrating "figure of 8" re-entry likely involving the septal fascicle. One patient presented with systolic dysfunction associated with a high premature ventricular complex burden, with the mechanism being bundle-to-bundle re-entrant beats masquerading as dual response to a single sinus impulse. Two patients were diagnosed with interfascicular re-entry. Diagnosis was aided by careful assessment of HV interval in sinus rhythm and ventricular tachycardia, multipolar catheters to assess the activation sequence of the His-right bundle branch, and fascicles and entrainment of different components of the HPS. Cure of the arrhythmia was achieved by ablation of the right bundle branch block in 3 patients, the left septal fascicle in 2 patients, and the left posterior fascicle in 1 patient.Proper diagnosis of re-entrant arrhythmias involving the HPS may prove challenging. We emphasize a structured approach for diagnosis and effective therapy.

Introduction: Fibrosis is an important contributor to atrial fibrillation (AF) substrate in heart failure, with TGF-β signaling generating atrial fibrosis. Inflammation is also known to contribute to AF. However, it is not known: a) if inflammation underlies the development of atrial fibrosis, b) if TGF-β signaling is involved in the generation of atrial inflammation and c) what is the relative role of canonical SMAD2/3 versus non-canonical TGF-β-activated kinase 1 (TAK) signaling in the creation of atrial inflammation/fibrosis. Methods: 21 dogs underwent transfection in the posterior left atria of either a plasmid expressing a dominant negative TGF-β type II receptor (pUBC-TGFβ-DN-RII) (N=9) or control vector (pUBC-LacZ) (N=12), followed by 3-4 weeks of right ventricular tachypacing (VTP) (240 bpm). After 3-4 weeks of VTP, the following were assessed: AF by open-chest mapping. Atrial tissue was assessed for signaling (pSMAD2/3 and pTAK) by western blot, fibrosis by trichrome staining and iflammation by CD68 staining. Results: The interstitial fibrosis in LacZ atria was replacement in character (Fig 1A). TGFβ-RII-DN dogs had a significant decrease in replacement fibrosis leading to a decrease in duration of inducible AF (LacZ 63.64 ± 12.12 s vs. TGFβ 26.52 ± 3.79 s, p < 0.05). While both groups demonstrated evidence of inflammation (CD68 staining), there was no difference in inflammation between the groups (Fig 1B). TGFβ-RII-DN dogs had a significant decrease in pSMAD2/3 but not pTAK, compared to pUBC-LacZ dogs. Conclusion: The development of fibrotic substrate for AF in advanced HF is driven not by inflammation but primarily by SMAD2/3 mediated myocardial replacement fibrosis. These findings may have important implications for mechanism-guided therapies for AF, with canonical TGF-β signaling appearing to be an attractive therapeutic target in AF.

Introduction: Dofetilide is a costly medication that requires hospitalization at initiation. Patterns of dofetilide use for the control of atrial fibrillation (AF) have not been reported. We sought to determine what percentage of dofetilide initiations at our institution were concordant with the tiered maintenance of sinus rhythm (MSR) algorithm for anti-arrhythmic drug (AAD) use outlined in the AHA/HRS guidelines for the management of AF. Methods: We performed a chart review of consecutive patients admitted for dofetilide initiation at our institution from 2004-09. Follow-up data were collected through November 2012. Patients were classified to mirror the MSR algorithm. Results: A total of 122 patients were included. The mean age was 62±13 years. The mean ejection fraction was 50% ± 12% and the average baseline sinus rate was 62±11bpm. Within the MSR classification, 36 patients had no significant structural heart disease, 12 had hypertension without LVH, 16 had hypertension with LVH, 18 had CAD without CHF, and 40 had CHF. In patients with no prior AAD exposure [56/122 (46%)], dofetilide use was significantly more discordant with the MSR guidelines than for patients in whom dofetilide was used as a second line agent [46% discordant vs 15% discordant, p Conclusions: A significant percentage of dofetilide use for the control of AF is as first-line AAD therapy. Electrophysiologists appear to be basing their choice of AAD on patient specific factors, such as baseline bradycardia, rather than the MSR algorithm. Given that the average duration of dofetilide therapy was little more than 2 years in AAD naïve patients, the cost-effectiveness of hospitalizing patients for dofetilide loading as a first line agent for the control of AF warrants further examination.

Background: Prolonged QT offset dispersion (QToD), an index of heterogeneity of ventricular repolarization, is thought to be an independent predictor of all-cause and cardiovascular mortality. However the influence of gender and autonomic tone in healthy adults on age-related changes in measures of ventricular repolarization are not well characterized. Methods: QToD and T wave complexity were measured in 56 healthy subjects with no detectable heart disease (by echo and stress test)—38 young subjects with a mean age of 28 ± 4 years and 18 old subjects with a mean age of 71 ± 7 years. QToD and T wave complexity were computed from 12-lead ECGs using the GE Marquette QT Guard automated analysis program with manual over-reading at rest (baseline), following exercise, and double autonomic blockade with atropine and propranolol. Data was analyzed using factorial ANOVA. Results: Young males had a significantly greater QToD than young and old females at baseline (28 ± 5 ms, 23 ± 5 ms, and 22 ± 5 ms, respectively, P < 0.01), an intrinsic effect independent of changes in autonomic tone. In contrast, females had significantly greater T wave complexity than males following exercise and double autonomic blockade with a definite trend at baseline. There was no correlation between T wave complexity and QToD. Conclusions: Age and gender demonstrate a complex interaction on indices of myocardial repolarization with different measures behaving differently. These findings have implications for better understanding age and gender effects on myocardial electrophysiology. A.N.E. 2001;6(4):290–297

Excitable Gap in Infarcted Canine Myocardium.Introduction: The existence of an excitable gap during ventricular fibrillation (VF) has been suggested in several prior studies. However, the effects of myocardial infarction on the presence and duration of an excitable gap during VF have not been evaluated. Methods and Results: Electrophysiologic study was performed in normal dogs and in dogs with subacute and chronic infarction. Experimental infarction was produced by left anterior descending coronary ligation. The excitable gap was determined indirectly using either evaluation of intrinsic wavefronts during VF or from the shortest activation interval at individual sites using recordings from a 112- electrode plaque sutured to the epicardial surface of the left ventricle. The excitable gap also was correlated to local electrophysiologic and anatomic properties. The excitable gap using the wavefront propagation method and shortest activation method was significantly longer in subacute infarction dogs (48 ± 17 msec and 37 ± 18 msec, respectively) and chronic infarction dogs (41 ± 14 msec and 35 ± 14 msec, respectively) than normal dogs (32 ± 13 msec and 30 ± 11 msec, respectively; P < 0.05 normal vs subacute and chronic infarction dogs in both methods). The excitable gap occupied approximately 30% and 27% of the VF cycle length in all three groups using the wavefront propagation and shortest activation method, respectively. The excitable gap correlated better with local ventricular refractoriness determined using the wavefront propagation method than with the shortest activation method, but not at all with refractoriness determined using extrastimulus testing. Tissue necrosis was noted in subacute infarction dogs and fibrosis in chronic infarction dogs, but the gap was not highly correlated with anatomic changes. Conclusion: During VF, an excitable gap exists in both normal and infarcted canine ventricular myocardium. It is significantly longer in the presence of infarction. These finding have implications for understanding the pathophysiology of VF and targeting antiarrhythmic therapies.

Percutaneous catheter ablation using radiofrequency energy can be used to interrupt atrioventricular (AV) conduction in patients with supraventricular tachycardia refractory to drugs. Results of radiofrequency ablation of the AV junction using a custom-designed catheter with a large, 3-mm-long distal electrode, 2-mm interelectrode spacing, and a shaft with increased torsional rigidity were compared with those using a standard quadripolar electrode catheter (Bard EP). An electrocoagulator (Microvasive Bicap 4005) supplied unmodulated radiofrequency current at 550 kHz, which was applied between the distal electrode of the ablation catheter and a large skin electrode. With use of the modified catheter, 12 of 13 patients (92%) had persistent complete AV block induced with 7 +/- 5 applications of 18 +/- 6 W of radiofrequency power. In contrast, complete AV block was produced in only 9 of 18 (50%) historical control patients treated with the standard catheter, despite a similar number of applications (7 +/- 5) and power output (16 +/- 4 W). A rise in impedance, due to desiccation of tissue and coagulum formation, occurred earlier (28 +/- 18 vs 52 +/- 24 seconds, p less than 0.001) and more frequently (54 vs 40% of applications, p = 0.047) in patients treated with the standard catheter than in patients treated with the modified catheter. The use of a catheter designed to increase the surface area of electrode-tissue contact allows more radiofrequency energy to be delivered before a rise in impedance occurs and appears to increase the effectiveness of radiofrequency ablation of the AV junction.

Background: The sympathetic nervous system (SNS) is thought to play an important role in promoting atrial fibrillation (AF) initiation and maintenance, especially in the setting of congestive heart failure (CHF). However, it is unclear as to which components of the SNS are altered in atria isolated from failing hearts. These studies are essential, as they will delineate potential molecular targets that may be probed for therapeutic intervention in order to reduce AF pathogenesis. Methods : CHF was induced by ventricular tachypacing (240 beats/minute) for 4 weeks in hound dogs. A total of 4 CHF and 5 control dogs were used. Immunoblot analysis was performed on left atrial appendage (LAA) homogenates to examine the protein expression of Gsα, Gi2α, and the catalytic subunit of protein kinase A (PKA). Catalytic activities of PKA and protein phosphatase type 2a (PP2a) were determined using non-radioactive enzyme activity assay systems. Cyclic AMP (cAMP) accumulation was assessed by an enzyme linked immunoabsorbant assay and phosphorylation of cardiac troponin I (cTnI) was determined using a phosphospecific antibody against cTnI. Results: Gsαconcentrations were increased approximately 4-fold in failing left atrial preparations relative to control. In contrast, expression of Gi2αwas modestly increased ~1-fold in failing LAA relative to non-failing atrial muscles. PKA activity was significantly increased in failing LAA preparations compared to control (124.7 vs. 42.1 pmole phosphate/minute, P P Conclusions: Our data are the first to characterize sympathetic remodeling in left atrial muscles isolated from an experimental model of CHF. Additionally, our results support the hypothesis that augmented sympathetic signaling and activation may contribute to the AF substrate in a canine model of CHF characterized by increased AF susceptibility.

Prior studies have found that there is a widespread practice of catheter reprocessing in cardiac electrophysiology laboratories. Effects of reprocessing of ablation catheters on temperature sensing and mechanical deflection are not fully known.Twenty-four new and used ablation catheters were studied. Deviation of temperature sensing by catheters from the temperature of a heated saline bath was measured. The angle of deflection of digitally scanned catheters at 75% and 100% handle deflection was also measured. New and used catheters were compared with respect to their temperature sensing accuracy and deflection characteristics.Overall, there was 0.7 +/- 0.1 degrees C (mean +/- standard error) deviation of the sensed temperature from the bath temperature, with no significant difference between new and used catheters. Similarly, there was no significant difference in the angle of deflection between new (66.7 degrees +/- 6.2 degrees and 24.3 degrees +/- 6.8 degrees at 75% and 100% deflections, respectively) and used (59.6 degrees +/- 5.6 degrees and 28.7 degrees +/- 9.9 degrees at 75% and 100% deflections, respectively) catheters. The difference in the angle of deflection between matched new and used catheters was 18.9 degrees +/- 4.2 degrees and 10.9 degrees +/- 2.4 degrees at 75% and 100% deflections, respectively, with a relatively broad range (5.0 degrees -35.6 degrees and 0.4 degrees -19.0 degrees at 75% and 100% deflections, respectively).This study found no significant overall difference in temperature sensing accuracy and deflection angle of new and used ablation catheters. Nevertheless, individual differences in deflection characteristics between new and used catheters are occasionally seen and warrant screening of reprocessed catheters prior to their reuse.

Background Although coronary atherosclerosis most commonly produces clinical effects as a result of stenosis, aneurysmal disease also occurs. We have found an increased prevalence of ectasia and aneurysmal disease in familial hypercholesterolemia (FH) suggesting a link between plasma lipoproteins and coronary aneurysms. Methods and Results In 197 asymptomatic subjects with FH, we examined the prevalence of ectasia and its association with coronary risk factors. An ectatic segment was defined as one with a luminal diameter >1.5 times that of the adjacent normal segment, excluding poststenotic dilation. Among subjects with FH, 15% had ectasia compared with 2.5% of an age- and sex-matched control group of 198 subjects without FH pre- senting for coronary angiography ( P P P =.003), a higher LDL/HDL ratio ( P =.003), and to a lesser extent, a higher LDL cholesterol level ( P =.07). No association was found with plasma triglycerides or very low-density lipoprotein cholesterol levels. Among FH patients, ectasia was strongly associated with an overall index of occlusive atherosclerotic disease, based on quantitative angiography ( P =.004). Intracoronary ultrasound interrogation of aneurysmal segments revealed circumferential intimal thickening. Conclusions Coronary ectasia is more prevalent in patients with FH than in other patients with coronary atherosclerosis and shows a strong inverse association with HDL cholesterol levels. This suggests that disordered lipoprotein metabolism in FH may predispose patients to aneurysmal coronary artery disease.

The protein CD36 is a membrane receptor for thrombospondin (TSP), malaria-infected erythrocytes, and collagen. Three functional sequences were identified within a single disulfide loop of CD36: one that mediates TSP binding (amino acids 87 to 99) and two that support malarial cytoadhesion (amino acids 8 to 21 and 97 to 110). One of these peptides (p87-99) is a consensus protein kinase C (PKC) phosphorylation site. Dephosphorylation of constitutively phosphorylated CD36 in resting platelets and a megakaryocytic cell line led to the loss of collagen adhesion and platelet reactivity to collagen, with a reciprocal increase in TSP binding. PKC-mediated phosphorylation of this ectodomain resulted in a loss of TSP binding and the reciprocal acquisition of collagen binding. In site-directed mutagenesis studies, when the threonine phosphorylation site was changed to alanine, CD36 was expressed in a dephosphorylated state and bound to TSP constitutively.

Application of ventricular premature complexes (VPCs) from the right ventricular (RV) apex during orthodromic atrioventricular (AV) reentrant tachycardia has limitations both in the ability to shorten the succeeding atrial cycle length and in helping to identify accessory pathway location. Stimulation from the summit of the RV aspect of the septum during AV reentrant tachycardia was investigated as a new technique to improve the diagnostic utility of applying VPCs during AV reentrant tachycardia. VPCs were induced during AV reentrant tachycardia at 10 ms decrements in patients with left free wall (n = 15), posteroseptal (n = 5), and right free wall (n = 3) accessory pathways from the RV apex and then from the summit of the RV septum. When the His was refractory, shortening of the atrial cycle length was noted in 13% of patients with left free wall pathways, in 60% of patients with posteroseptal pathways, and in 100% of patients with right free wall pathways with VPCs from the RV apex, and in 47,100 and 100%, respectively, with VPCs from the summit of the septum. When all VPCs were considered, there was a significant shortening of the atrial cycle length in 67% of patients with left free wall pathways when stimulated from the RV apex, which increased to 93% with summit stimulation. An extrastimulus applied on or after the His effected a significant shortening of the atrial cycle length in no patients with left free wall pathways. The mean maximal shortening of the atrial cycle length when the His was refractory was 4 ± 11 and 9 ± 13 ms for left free wall pathways, 29 ± 30 and 40 ± 11 ms for posteroseptal pathways, and 35 ± 15 and 53 ± 35 ms for right free wall accessory pathway from the apex (p = 0.006) and summit (p = 0.0002), respectively. Stimulation of the summit of the RV septum improves the ability of VPCs to shorten the atrial cycle length during AV reentrant tachycardia.

To evaluate the ability of two-dimensional echocardiographic indexes to determine the hemodynamic significance of the right ventricular infarction, 24 patients with electrocardiographic evidence of right ventricular infarction were studied. Hemodynamic significance was defined as a jugular venous pressure greater than 17 cm H2O or a right atrial pressure greater than 13 mm Hg. Patients with hemodynamically significant right ventricular infarctions (group I, n = 9) had a 56% incidence of hypotension (blood pressure less than 90 mm Hg) with a mean systolic blood pressure of 93 +/- 23 mm Hg, whereas patients with nonhemodynamically significant right ventricular infarctions (group II, n = 15) had no hypotension and a mean systolic blood pressure of 121 +/- 18 mm Hg (p less than 0.01). The ratio of right atrial to pulmonary capillary wedge pressure was 1.1 +/- 0.6 in group I and 0.6 +/- 0.2 in group II (p less than 0.05). Echocardiography demonstrated right ventricular free wall motion abnormalities in seven patients in group I and in 10 patients in group II. The descent of the right ventricular base was 0.7 +/- 0.2 cm in group I, 1.3 +/- 0.4 cm in group II, and 2.0 +/- 0.2 cm in a group of 20 normal control patients (p less than 0.001 for all comparisons). The respiratory caval index (percentage of collapse of the inferior vena cava with inspiration) was 22% +/- 11% in group I, 45% +/- 15% in group II, and 64% +/- 17% in the control subjects (p less than 0.05 for all comparisons).(ABSTRACT TRUNCATED AT 250 WORDS)

BACKGROUND The utility of transcatheter application of radiofrequency energy to eliminate atrioventricular nodal reentrant tachycardia (AVNRT) was investigated. METHODS AND RESULTS Thirty-nine patients (mean age, 53 +/- 20 years; range 14-86 years) with medically refractory AVNRT underwent perinodal ablation with radiofrequency energy. A custom-designed 6F catheter with a large (3-mm-long) distal electrode and interelectrode pacing of 2 mm was used in the majority of cases. The catheter used for ablation was initially positioned across the tricuspid anulus to obtain the largest His bundle electrogram, then withdrawn to obtain the largest atrial:ventricular electrogram ratio, with a small His bundle electrogram (less than or equal to 100 microV). Each application of radiofrequency energy (350-550 kHz, 16.2 +/- 5.2 W) was stopped after 60 seconds or if PR prolongation or an impedance rise was noted. The endpoints of the procedure were persistent modification of atrioventricular nodal conduction (either first-degree atrioventricular block or impairment of ventriculoatrial conduction) and noninducibility of AVNRT before and during isoproterenol administration. Radiofrequency energy was applied a mean of 6.8 +/- 3.5 times per session. After a mean follow-up of 8 +/- 3.0 months, 32 of the 39 patients (82%) have been free of AVNRT, and did not have high grade AV block. Three patients (8%) developed complete atrioventricular block and had pacemakers implanted. Two patients had unsuccessful initial procedures, and two patients had initially successful ablations but had recurrences of tachycardia 4-6 weeks later. Elimination of AVNRT appeared to be due to effects on the retrograde fast pathway in most patients. CONCLUSIONS Radiofrequency ablation of the perinodal right atrium appears to be safe and effective for treatment of typical AVNRT

The clinical utility of nifedipine and diltiazem blood levels in patients with angina pectoris receiving monotherapy (N = 14) and combination treatment (N = 9) were assessed in a placebo run-in, double blind, randomized, crossover study. Compared to placebo, diltiazem (mean daily dose 360 mg), nifedipine (mean daily dose 90 mg) and combination diltiazem-nifedipine therapy (mean daily dose 55 mg of nifedipine, 360 mg of diltiazem) were associated with reductions in weekly angina attacks and nitroglycerin consumption. Although both drugs used as monotherapy and in combination were also associated with significant increments in exercise tolerance and other improved angina parameters, these changes were not related to the plasma levels of either drug. Nifedipine plasma levels were measured by gas chromatography and diltiazem plasma levels measured by reverse high-pressure liquid chromatography from specimens obtained 2-5 hours after the last previous dose, after 1, 2 and 3 weeks of treatment, and during baseline placebo and placebo washout periods. With combination therapy, there was no effect on the diltiazem plasma level compared to monotherapy. The significant decrease in the nifedipine dose in patients on combination therapy did not significantly change nifedipine plasma levels. Determinations of plasma levels of diltiazem and nifedipine in the management of patients is of no value in the management of patients with angina pectoris except for monitoring treatment compliance and overdosage.

Calcium-channel blockers have been successfully used in the treatment of angina of effort and systemic hypertension. Many patients present with concomitant angina pectoris and hypertension. Controlled clinical trials demonstrate that the calcium-channel blockers are safe and effective as monotherapy in the treatment of these patients, and that their use compares favorably with that of propranolol. The effectiveness of these agents in hypertension appears to be primarily due to their ability to induce systemic vasodilation. Calcium-channel blockers have several therapeutic effects in angina pectoris. Beneficial actions on the major determinants of oxygen consumption, i.e. heart rate, blood pressure and contractility, are generally seen. The potent coronary vasodilating actions of these agents allow for increased coronary blood flow. Improvements in ventricular compliance, regression of left ventricular hypertrophy and cardioprotection appear to be additional effects of the calcium-channel blockers; their contribution to the drugs' overall therapeutic efficacy is presently being evaluated. Calcium-channel blockers are a welcome addition to drug regimens available for the management of patients with coexisting angina pectoris and hypertension.

In a randomized, double-blind, placebo-controlled crossover trial, diltiazem and nifedipine were compared in 10 patients with stable angina pectoris and mild to moderate hypertension (supine diastolic blood pressure greater than or equal to 90 mm Hg). Patients received placebo for 2 weeks, then increasing doses of diltiazem (90 to 360 mg/day) or nifedipine (30 to 120 mg/day) in 3 daily divided doses over 2 weeks, followed by 1 week of therapy at the maximal dose, a 1-week placebo "washout," then crossover to the other drug. Heart rate and blood pressure at rest and during exercise, anginal frequency, nitroglycerin consumption and treadmill exercise tolerance were assessed. Compared with placebo, anginal frequency and nitroglycerin consumption were reduced with both diltiazem and nifedipine (p less than 0.01) and exercise tolerance was increased with both drugs (p less than 0.01). Standing blood pressure at rest was reduced by diltiazem and nifedipine (146.6 +/- 11.4/97.7 +/- 5.3 mm Hg at placebo, baseline reduced to 129.6 +/- 15.2/79.5 +/- 13.7 mm Hg with diltiazem, and to 122.2 +/- 9.9/82.0 +/- 7.1 with nifedipine, p less than 0.01 for both). Compared with placebo, diltiazem and nifedipine also reduced exercise diastolic blood pressure (p less than 0.01), but not systolic blood pressure. Diltiazem lowered the heart rate at rest from 88.5 +/- 14.4 beats/min at placebo baseline to 79.7 +/- 17.9 beats/min (p less than 0.01); the heart rate with diltiazem was 11 beats/min lower than that with nifedipine (p less than 0.05). Both diltiazem and nifedipine had similar effects on the heart rate-blood pressure product at rest and during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial infarction has been a relatively understudied entity. Its incidence by autopsy study has been widely variable, from 0.7% to 42%, with the largest series of 182 patients demonstrating an incidence of 17%. The right atrium is involved five times as often as the left, with the auricle the predominant site in either atria. Clinical atrial infarction may present with supraventricular arrhythmias, atrial rupture, hemodynamic compromise from loss of atrial "kick," and thromboembolic phenomena. Diagnosis currently is made in an appropriate clinical setting with characteristic PR interval changes. Other noninvasive techniques have shown only limited diagnostic utility, but esophageal echocardiography may prove to be a useful technique in this setting.