Pulmonary Tumor Thrombotic Microangiopathy with Administration of Pulmonary Vasodilator Resulting in Clinical Improvement Prior to Final Diagnosis.

BACKGROUND The pathophysiology of pulmonary tumor thrombotic microangiopathy (PTTM) was recently revealed by autopsy. Considered rare, we suggest that this fatal disease is not rare, but has not been diagnosed pre-mortem. Some patients with pulmonary thromboembolism with unknown thrombus source or with sudden death have been treated for malignant carcinoma. We report a patient with PTTM who was successfully rescued acutely by treatment with soluble guanylate cyclase (sGC), resulting in appropriate palliative care. CASE REPORT An 80-year-old Japanese woman was transferred to our emergency room for severe dyspnea owing to type I respiratory failure. Her clinical findings indicated pulmonary thromboembolism, but we found no thrombus in either the pulmonary artery or inferior vena cava. However, we incidentally found gallbladder cancer with peritoneal metastases. These findings raised the suspicion of PTTM. We began concurrent sGC and direct oral anticoagulant (DOAC) on the assumption that PTTM had occurred, while performing peripheral pulmonary artery sampling for cytology, and pulmonary perfusion scintigraphy. Cytology revealed several aplastic cells; consequently, we finally diagnosed PTTM. Because she did not wish to undergo examination and active treatment for carcinoma, we initiated palliative care while continuing sGC. She was able to spend time with her family for more than 100 days, without dyspnea. CONCLUSIONS We must recognize PTTM, which is a lesser-known disease, and introduce diagnostic therapy with a pulmonary vasodilator, such as sGC, immediately, when we suspect PTTM, leading to appropriate clinical care.

Influence of cognitive impairment on cardiac mortality after percutaneous coronary intervention in very elderly patients: a retrospective observational study.

BACKGROUND: Cognitive impairment (CI) increases cardiac mortality among very elderly patients. Percutaneous coronary intervention (PCI) for ischemic heart disease (IHD) patients is considered a favorable strategy for decreasing cardiac mortality. Here, we investigated the influence of CI on cardiac mortality after PCI in very elderly patients. METHODS: We performed a retrospective observational analysis of patients who received PCI between 2012 and 2014 at the South Miyagi Medical Center, Japan. IHD patients over 80 years old who underwent the Mini-Mental State Examination for CI screening during hospitalization and/or who had been diagnosed with CI were included. Participants were divided into CI and non-CI groups, and cardiac mortality and incidence of adverse cardiac events in a 3-year follow-up period were compared between groups. Statistical analyses were performed using the t-test, χ2 test, and multivariable Cox regression analysis, with major comorbid illness and conventional cardiac risk factors as confounders. RESULTS: Of 565 patients, 95 were included (41 CI, 54 non-CI). Cardiac mortality during the follow-up period was significantly higher in the CI group (36%) compared with the non-CI group (13%) (OR = 4.3, 95% CI: 1.56-11.82, P < 0.05). CI was an independent cardiac prognostic factor after PCI and, for CI patients, living only with a CI partner was an independent predictor of cardiac death within three years. CONCLUSIONS: CI significantly affected cardiac prognosis after PCI in very elderly patients, particularly those living with a CI partner. To improve patients' prognoses, social background should be considered alongside conventional medical measures.

Influence of atrial fibrillation on cardiac prognosis in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD), a known risk factor for the development of congestive heart failure (CHF), was recently shown to predict the prevalence of atrial fibrillation (AF). Here, we explore the influence of AF on cardiac prognosis in COPD patients. METHODS: A total of 339 consecutive patients who underwent spirometry from 2010 to 2013 for various reasons were retrospectively examined. Based on the diagnostic criteria, patients were stratified into COPD and non-COPD groups, which were both further divided into those with AF (chronic AF or paroxysmal AF) or sinus rhythm (SR) based on previous electrocardiography results. Significances of differences in cardiac events were assessed by the chi-square test. Multivariate logistic regression analyses and Cox proportional hazard models were applied to evaluate the influence of AF on cardiac events. RESULTS: Of the 339 patients, 190 were diagnosed with COPD, with 42 of these were having AF. During the mean follow-up period of 7.4 ± 0.8 years, CHF developed more frequently in COPD patients with AF than in COPD patients without AF [50% vs 7%; odds ratio (OR) 12.4, 95% confidence interval (CI): 5.25-29.49, p < 0.05]. AF was an independent predictor of CHF development (OR 20.4, 95% CI: 6.55-79.80, p < 0.05) and cardiac mortality (OR 2.8, 95% CI: 1.79-4.72, p < 0.05). Moreover, positive correlations were found between the severity of pulmonary obstruction with AF and CHF development (R = 0.69, p < 0.05), as well as cardiac mortality (R = 0.78.p < 0.05). CONCLUSIONS: These results suggest that AF may be strongly associated with cardiac mortality and CHF in COPD patients.

Recurrent Acute Myocardial Infarction in a Patient with Severe Coronary Artery Ectasia: Implication of Antithrombotic Therapy.

BACKGROUND Acute myocardial infarction (AMI) can be caused not only by plaque rupture/erosion, but also by many other mechanisms. Thromboembolism due to atrial fibrillation and coronary thrombosis due to coronary artery ectasia are among the causes. Here we report on a case of recurrent myocardial infarction with coronary artery ectasia. CASE REPORT Our case was a 78-year-old woman with hypertension. Within a one-month interval, she developed AMI twice at the distal portion of her right coronary artery along with coronary artery ectasia. On both events, emergent coronary angiography showed no obvious organic stenosis or trace of plaque rupture at the culprit segment after thrombus aspiration. After the second acute event, we started anticoagulation therapy with warfarin to prevent thrombus formation. In the chronic phase, we confirmed, by using coronary angiography, optimal coherence tomography and intravascular ultrasound, that there was no plaque rupture and no obvious thrombus formation along the coronary artery ectasia segment of the distal right coronary artery, which suggested effectiveness of anticoagulant. Furthermore, by Doppler velocimetry we found sluggish blood flow only in the coronary artery ectasia lesion but not in the left atrium which is generally the main site of systemic thromboembolism revealed by transesophageal echocardiography. CONCLUSIONS These results suggest that the two AMI events at the same coronary artery ectasia segment were caused by local thrombus formation due to local stagnant blood flow. Although it has not yet been generally established, anticoagulation therapy may be effective to prevent thrombus formation in patients with coronary artery ectasia regardless of the prevalence of atrial fibrillation.

Hypercholesterolemia impairs transduction of vasodilator signals derived from ischemic myocardium: myocardium-microvessel cross-talk.

OBJECTIVE: Coronary microvessels are functionally coupled to the myocardial metabolic state. In hypercholesterolemia, the coronary vascular dysfunction extends to microvascular levels. We hypothesized that the vasodilator signal transduction from ischemic heart is impaired in the coronary microvascular wall of hypercholesterolemia. METHODS AND RESULTS: Rabbits were fed with normal chow (control group) or 2% high-cholesterol diet (hypercholesterolemia group) for 8 weeks. Coronary microvessels isolated from rabbit hearts were pressurized and gently placed on a beating canine heart. Myocardial ischemia was produced in the beating heart and the diameter of the isolated microvessel was observed using an intravital microscope with a floating objective. In control group, the isolated microvessels significantly dilated 2 minutes after the onset of ischemia, and a plateau was observed at 10 minutes. In contrast, the microvessels from hypercholesterolemia group did not dilate during ischemia. Dihydroethidium fluorescence microscopy revealed an elevated superoxide level in the microvessels of hypercholesterolemia group. The application of tiron (free radical scavenger) significantly dilated the isolated microvessels only from hypercholesterolemic animals. CONCLUSIONS: We conclude that the transduction of vasodilator signals derived from ischemic myocardium is impaired in the coronary microvascular wall of hypercholesterolemia. Enhanced oxidative stress in hypercholesterolemia may alter the microvascular function.

Impact of hypercholesterolemia on acidosis-induced coronary microvascular dilation.

An increase in coronary flow conductance during acidosis is an important compensatory mechanism in various diseased conditions. On the other hand, hypercholesterolemia causes microvascular dysfunction as well as macrovascular disorders. We investigated the impact of hypercholesterolemia on the coronary microvascular response to acidosis. Coronary arterioles (< 150 microm) isolated from rabbit hearts were cannulated to micropipettes in a vessel chamber and the microvascular responses were observed. After preconstriction was established, the extravascular pH was gradually reduced from 7.4 to 7.0. The effects of glibenclamide, ATP-sensitive K(+) (K(ATP)) channel blocker, (1 microM, n = 4) or pertussis toxin (100 ng/mL, n = 7) on the acidosis-induced microvascular responses were examined. In another set of experiments, rabbits were randomly assigned to normal chow (NC group, n = 18) or high cholesterol (2 %) diet (HC group, n = 20). After 8 weeks of feeding, the responses of isolated coronary arterioles to acidosis, ADP, nitroprusside, and levcromakalim were examined in the two groups. Coronary arterioles significantly dilated as the pH was reduced and the dilation was significantly inhibited by glibenclamide or pertussis toxin. Acidosis-induced dilation in the HC group was significantly attenuated compared to the NC group (36.5 +/- 2.1 % vs 73.7 +/- 4.8 % at pH = 7.0 P < 0.05). There were no significant differences in the dilations by ADP, nitroprusside and levcromakalim between the two groups. In conclusion, acidosis-induced dilation of rabbit coronary arterioles is mediated by the activation of the pertussis toxin-sensitive G protein and K(ATP) channels, and the dilation of coronary arterioles is impaired in hypercholesterolemia. The impairment occurs upstream of K(ATP) channel opening.

Vasodilator signals from the ischemic myocardium are transduced to the coronary vascular wall by pertussis toxin-sensitive G proteins: a new experimental method for the analysis of the interaction between the myocardium and coronary vessels.

OBJECTIVES: We sought to detect cross-talk between the beating heart and coronary vascular bed during myocardial ischemia and to test the hypothesis that the cross-talk is mediated by pertussis toxin (PTX)-sensitive G proteins (G(PTX)) in vessels. BACKGROUND: Coronary flow is closely related to the myocardial metabolic state, indicating the existence of a close interaction between cardiac muscle and coronary vascular beds. Experimental methods for the analysis of the interaction, however, have not been established. METHODS: Coronary detector vessels (DVs) were isolated from rabbit hearts. One end of the vessel was cannulated to a micropipette, and the other end was ligated. After the DV was pressurized (60 cm H(2)O), it was gently placed on the myocardium, which was perfused by the left anterior descending coronary artery (LAD) of anesthetized, open-chest dogs (n = 23). The LAD was occluded, and the DV diameter was observed using an intravital microscope with a floating objective system. To evaluate the involvement of G(PTX), the DV was pre-incubated with PTX (100 ng/ml). RESULTS: The LAD occlusion of the beating heart produced significant dilation of DVs (241 +/- 25 microm) by 10%. The DVs pretreated with PTX (250 +/- 27 microm) did not dilate in response to myocardial ischemia. N(omega)-nitro-L-arginine (100 micromol/l), but not glibenclamide (5 micromol/l), abolished the ischemia-induced DV dilation. CONCLUSIONS: We have established experimental methods for direct analysis of the interaction between the myocardium and coronary microvessels. We conclude that the ischemic myocardium releases transferable vasodilator signals that are transduced by means of the G(PTX) located in the vascular walls. The nitric oxide pathway is involved in the signal transduction.