Bi-allelic variants in the mitochondrial RNase P subunit PRORP cause mitochondrial tRNA processing defects and pleiotropic multisystem presentations.

Human mitochondrial RNase P (mt-RNase P) is responsible for 5' end processing of mitochondrial precursor tRNAs, a vital step in mitochondrial RNA maturation, and is comprised of three protein subunits: TRMT10C, SDR5C1 (HSD10), and PRORP. Pathogenic variants in TRMT10C and SDR5C1 are associated with distinct recessive or x-linked infantile onset disorders, resulting from defects in mitochondrial RNA processing. We report four unrelated families with multisystem disease associated with bi-allelic variants in PRORP, the metallonuclease subunit of mt-RNase P. Affected individuals presented with variable phenotypes comprising sensorineural hearing loss, primary ovarian insufficiency, developmental delay, and brain white matter changes. Fibroblasts from affected individuals in two families demonstrated decreased steady state levels of PRORP, an accumulation of unprocessed mitochondrial transcripts, and decreased steady state levels of mitochondrial-encoded proteins, which were rescued by introduction of the wild-type PRORP cDNA. In mt-tRNA processing assays performed with recombinant mt-RNase P proteins, the disease-associated variants resulted in diminished mitochondrial tRNA processing. Identification of disease-causing variants in PRORP indicates that pathogenic variants in all three subunits of mt-RNase P can cause mitochondrial dysfunction, each with distinct pleiotropic clinical presentations.

Strategies to overcome challenges of transradial coronary angiography and intervention.

The transradial approach has become the preferred route for performing coronary angiography and interventions. Several studies reported that radial access is associated with significant reduction in vascular complications compared with the femoral access. This technique allows also early ambulation, improves the patient's well-being, and is less expensive. One important limitation of radial access is that coronary engagement from transradial approach is more challenging than transfemoral approach. The increased susceptibility of the radial artery to spasm, the radial-brachial artery tortuosities, and the subclavian-aorta curves make catheter advancement and coronary artery cannulation difficult. Hereby, we suggest several techniques for recognising and overcoming potential challenges during transradial coronary angiography.

Superior vena cava-right atrium junction flow-pattern post-transcatheter closure of patent foramen ovale.

BACKGROUND: The patent foramen ovale (PFO) occluder is a bulky metallic device. Its impact on the normal blood flow at the superior vena cava-right atrial (SVC-RA) junction is not clear. METHODS: We examined SVC-RA junction flow-pattern using pulsed-wave (PW) ultrasound Doppler in 21 patients (4 male, aged 52.7 ± 9 years) who underwent PFO device closure 4-120 months previously, in comparison with 21 age- and sex-matched controls (4 male, aged 51 ± 8.5 years) with structurally normal hearts. RESULTS: Mean systolic flow velocity at the SVC-RA junction was 60 ± 11 cm/s in the PFO closure group and 64 ± 17 cm/s in the control group (P = 0.27). Mean diastolic blood flow velocity at the SVC-RA junction in those groups was 30 ± 8 and 35 ± 9 cm/s, respectively (P = 0.1).The mean systolic wave duration was 439 ± 52 ms in the PFO closure group and 422 ± 67 ms in the control group (P = 0.4). The mean diastolic wave duration was 320 ± 75 and 277 ± 88 ms, respectively (P = 0.12). CONCLUSION: The study results show that transcatheter PFO closure does not affect the normal blood flow at the SVC-RA junction.

Biventricular Rupture with Extracardiac Left-to-Right Shunt Complicating Acute Myocardial Infarction.

BACKGROUND: Simultaneous rupture of the left and right ventricles is an extremely rare mechanical complication of acute myocardial infarction (MI). When associated with the formation of a false aneurysm, an extracardiac left-to-right shunt may occur. METHODS: We summarized all published data describing this unique condition. We searched the PubMed and Google Scholar databases for case reports in peer-reviewed journals from 1 January 1980 to 1 May 2015. We identified 16 articles describing 17 cases. RESULTS: In all but 1 case, biventricular wall rupture (BVWR) resulted from an inferior MI. The clinical presentations of BVWR were variable and included cardiogenic shock, congestive heart failure and an absence of any cardiac symptoms. In most cases, there was a hemodynamically significant left-to-right shunt, with pulmonary to systemic blood flow (Qp/Qs) >2. Diagnostic difficulties were reported in most cases, and some patients were initially misdiagnosed as having ventricular septal rupture (VSR). Surgical closure of the defect was successful in most cases, and some asymptomatic patients were managed conservatively. CONCLUSION: BVWR with an intact interventricular septum and extracardiac left-to-right shunt is a rare mechanical complication of acute MI, often misdiagnosed as VSR. It has a variable clinical course, probably related to the magnitude of the shunt.

A randomized study comparing the use of a pelvic lead shield during trans-radial interventions: Threefold decrease in radiation to the operator but double exposure to the patient.

OBJECTIVES: To determine the efficacy of a 0.5-mm lead apron across the patient's abdomen in addition to standard operator protection for the reduction of scatter radiation on operator and patient radiation exposure BACKGROUND: Cardiac angiography using the radial access compared to the femoral approach is associated with reduced complication rate and improved patient comfort but has significantly increased radiation dose. Improvements in radiation protection are needed METHODS: We randomly assigned 332 patients undergoing coronary angiography to a group with pelvic lead shielding and a group with standard protection. In each procedure, eight digital dosimeters were used to measure operator radiation dose [under the lead apron, outside the thyroid shield, and at the left side of the head], patient dose at the level of the umbilicus [above and beneath the lead apron], and two on the acrylic shielding and one on the image receptor to measure scattered radiation RESULTS: Both groups were similar in BMI, procedures performed, and number of sequences. Usage of lead shielding statistically significantly reduced the radiation dose of the operator at all three sites measured: under lead apron [all in µSv]: 0.53 ± 1.4 vs. 0.17 ± 0.6, on thyroid collar 5.9 ± 7.7 vs. 2.9 ± 3.4, and left side of head 3.3 ± 3.4 vs. 2.1 ± 2.2, P<0.001. However the radiation to the patient was doubled from 15.4 ± 24.1 to 28.9 ± 81.1, P=0.04 CONCLUSIONS: The use of a pelvic lead shield during radial angiography reduced the operator radiation exposure at multiple measurement sites. However there was an increased exposure to the patient. This balance should be further investigated before the widespread adoption of this method. .

Increased incidence of coronary artery origin anomalies associated with isolated patent ductus arteriosus.

Coronary artery anomalies may increase the risk of sudden death. Despite awareness of this association with certain congenital heart anomalies such as tetralogy of Fallot and transposition of the great arteries, it is thought to be an infrequent finding in cases of isolated patent ductus arteriosus (PDA). The authors report their experience with coronary anomalies in PDA patients. This study aimed to estimate the incidence of coronary artery anomalies in patients with PDA. The study reviewed 206 angiograms of PDA patients obtained between 1999 and 2011 to determine the origin of the coronary arteries. In 102 angiograms (49.5 %), the origin of the coronary arteries could be adequately visualized. An anomalous origin of coronary arteries was detected in 11 of the 102 patients (10.8 %). Seven of these patients had a single common coronary artery origin (6.8 %). One patient had an aberrant origin of the left coronary artery from the noncoronary sinus, and three patients had an aberrant origin of the right coronary artery: two from the left coronary sinus and one from the noncoronary sinus. These findings suggest that the incidence of coronary artery anomalies in association with an isolated PDA may be considerably higher than expected and previously reported. In view of the increased risk for sudden death with coronary anomalies, a reasonable approach is to determine the coronary artery origin and pathway after the diagnosis of an isolated PDA.

Transcatheter Closure of a Iatrogenic Gerbode Type Ventricular Septal Defect Post Surgical Septal Myectomy With Mitral and Aortic Valve Replacement.

Jatrogenic communication between left ventricle and right atrium, known as Gerbode type ventricular septal defect (GVSD) may be observed after different surgical interventions. We present a case of iatrogenic GVSD following complex cardiac surgery including septal myectomy combined with mitral and aortic valve replacement, which was successfully closed percutanously by Occlutech septal occluder.

Acute Effects of Insulin on Cardiac Function in Patients with Diabetes Mellitus: Clinical Applicability and Feasibility.

BACKGROUND: Insulin promotes glucose consumption as the main cardiac energy source, while increasing myocardial efficiency. The short-term effects of insulin on cardiac function and its potential curative role in an acute diabetological cardiology setting remain unknown. Our study evaluated the role of acute insulin administration in the diabetic heart, its corresponding effective blood insulin level, and the time-course applicability of insulin treatment in a routine clinical setting. METHODS: We evaluated a case series of six male (48.1 ± 4.9 y/o) patients with controlled diabetes (HbA1c of 6.6 ± 0.3%) and disease duration of 14.4 ± 6.7 yr. Each subject was evaluated for glucose homeostasis, as well as hemodynamic and echocardiographic (systolic and diastolic) parameters at three points: baseline followed by two successive insulin loads in euglycemic hyperinsulinemic clamp study. Results were analysed using Student's t-test. RESULTS: The first insulin load led to a physiologic blood insulin level of 145 ± 36 µU/ml, and both systolic (7 mmHg) blood pressure and diastolic (4 mmHg) blood pressure decreased significantly. Left ventricular fractional shortening (LVFS) increased significantly by 11.8%. Diastolic function parameters of mitral annulus movement of the A' wave increased relative to baseline by 20.0% (27.8% under the second insulin load), A' medial increased relative to baseline by 30%, and A' lateral increased relative to baseline by 17%, displayed by tissue Doppler imaging. CONCLUSIONS: Insulin acutely affected the diabetic heart at a physiologic level within a 2 h time course. Insulin mainly increased left ventricular systolic function and, to a second degree, improved left ventricular diastolic functions and atrial systole in diabetic subjects. These results may facilitate the development of insulin-based acute treatment in diabetic patients with cardiac morbidity. This trial is registered with NCT02962921.

Novel Technique for the Treatment of Coronary Artery Perforation.

Coronary artery perforation is a rare complication of percutaneous coronary intervention (PCI); its rate is estimated at 0.4- 0.7% of all PCIs. Fast recognition and response are imperative for the treatment of this potentially life-threatening complication. Available techniques for the treatment of perforations have moderate success rates and often necessitate dedicated equipment and expertise. In the case report presented, we describe a novel technique used to treat coronary perforations with readily available equipment.

The effect of TEE on treatment change in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Ischemic stroke is a widespread disease carrying high morbidity and mortality. Transesophageal echocardiography (TEE) is considered an important tool in the work-up of patients with acute ischemic stroke (AIS) and transient ischemic attack (TIA) patients; its utility is limited by a semi-invasive nature. The purpose of this study was to evaluate the probability of treatment change due to TEE findings (yield) in the work-up of AIS and TIA patients. METHODS: Retrospective data on patients with AIS or TIA who underwent TEE examination between 2000-2013 were collected from the institutional registry. RESULTS: The average age of 1284 patients who were included in the study was 57±10.4, 66% of patients were male. The most frequent TEE findings included aortic plaques in 54% and patent foramen ovale (PFO) in 15%. TEE findings led to treatment change in 135 (10.5%) patients; anticoagulant treatment was initiated in 110 of them (81%). Most common etiology for switch to anticoagulation was aortic plaques (71 patients); PFO was second most common reason (26 patients). Significant TEE findings (thrombus, endocarditis, tumor) were found in 1.9% of patients, they were more common in young patients (<55; 56% of the patients). CONCLUSIONS: The beginning of anticoagulation treatment in patients with thick and complicated plaques was found frequently in our study. Significant TEE findings, were infrequent, constituted an absolute indication for treatment change and were more common in younger patients.

Type of Anemia, Chronic Non-cardiovascular Illnesses, and Outcomes of Patients with ST-segment Elevation Myocardial Infarction.

OBJECTIVES: To assess the impact of different types of anemia and of concomitant non-cardiovascular chronic illnesses on outcomes of patients with ST-segment elevation myocardial infarction (STEMI) and baseline anemia admitted to the Intensive Cardiac Care Unit. METHODS: Based on the mean corpuscular volume, anemia was stratified into: microcytic (<80 fL), normocytic (≥80, <96 fL), and macrocytic (≥96 fL). Data on concomitant chronic non-cardiovascular illnesses including malignancies were carefully collected. Endpoints included in-hospital bleeding as well as all-cause mortality at long-term follow-up. RESULTS: Of 1,390 patients with STEMI, 294 patients had baseline anemia (21.2%), in whom normocytic, microcytic, and macrocytic anemia was present in 77.2%, 17.0%, and 5.8% patients, respectively. In-hospital bleeding occurred in 25 (8.5%) of the study population without significant differences between the three groups. At a mean follow-up of 5.5±3.5 years, 104 patients (35.4%) had died. Mortality was the highest in patients with macrocytic anemia, followed by patients with normocytic anemia and microcytic anemia (58.8%, 37.0%, and 20.0%, respectively; P=0.009). Chronic non-cardiovascular condition was identified as an independent predictor of both in-hospital bleeding (odds ratio=2.57, P=0.01) and long-term mortality (hazard ratio [HR] 1.54, P=0.019). Performance of coronary angiography within index hospitalization was associated with lower long-term mortality (HR 0.38, P=0.001). Mean corpuscular volume did not predict either in-hospital bleeding or mortality. CONCLUSIONS: Chronic non-cardiovascular illnesses are highly prevalent among patients with STEMI and baseline anemia, and are strongly associated with higher in-hospital bleeding and long-term mortality. Type of anemia is not related to prognosis post-STEMI.

Late high degree atrioventricular block after percutaneous closure of a perimembranous ventricular septal defect.

Atrioventricular block is an important complication after percutaneous closure of perimembranous ventricular septal defects. In the majority of cases, it appears in early or in the midterm of closure. We present a patient who developed symptomatic Mobitz 2 second-degree atrioventricular block 3 years following percutaneous closure of such a defect.

Occluded mammary graft post-coronary bypass surgery: do we need to look for the second one? A case report.

BACKGROUND: Anatomic variations of the left internal mammary artery (LIMA) can influence coronary artery bypass surgical technique as well as posing definite difficulties in the interpretation of angiographic findings. We present an unusual anatomic variant of two LIMAs originating from the left subclavian artery discovered post-coronary artery bypass grafting surgery. CASE SUMMARY: A 60-year-old man post-LIMA grafting of the left anterior descending (LAD) coronary artery underwent diagnostic cardiac catheterization. Selective angiography revealed occluded LIMA; therefore, it was decided to proceed with percutaneous coronary intervention (PCI) to the occluded native LAD. Once antegrade flow in the LAD was restored, retrograde filling of a vessel corresponding to the previously grafted LIMA was also detected. Additional contrast injection in the left subclavian artery (LSCA) showed a second patent LIMA originating from the distal segment of the LSCA. DISCUSSION: This patient has an unusual anatomic variant of two LIMAs originating from the LCSA. The proximal rudimentary LIMA was misinterpreted as an occluded arterial graft while the second, well-developed LIMA connected to the LAD had an unusually distal origin and had therefore been overlooked. This anatomical variant should be kept in mind when the internal mammary graft seems to be occluded.

Appropriateness of diagnosis of unstable angina pectoris in patients referred for coronary arteriography.

BACKGROUND: A diagnosis of unstable angina pectoris (UAP) often carries with it a decision to catheterize the patient promptly. However, UAP remains a clinical diagnosis, based mostly on a patient's clinical history and electrocardiogram (ECG) findings. OBJECTIVE: To evaluate whether the diagnosis of UAP is overused in patients referred for coronary arteriography. METHODS: Ninety-six patients with a diagnosis of UAP who were referred for invasive studies were re-examined clinically before catheterization. Coronarography was independently reviewed for correlation with clinical findings. RESULTS: Based on the patient's history and ECG changes, UAP was classified by two independent cardiologists as 'very likely' in 58% and 49%, 'possible' in 19% and 30%, and of 'low probability' in 23% and 21%, respectively. Patients with 'very likely' UAP had a high incidence of significant coronary lesions (87% and 96% for each cardiologist) and complex lesions by angiography (41% and 49%, respectively). Patients with a diagnosis of 'low probability' UAP had a low incidence of significant coronary lesions (55% for each cardiologist) and a very low incidence of complex angiographic lesions (5% for each cardiologist). Patients with 'possible' UAP had intermediate results. CONCLUSION: Because of a presumptive diagnosis of UAP, approximately 22% of all patients referred for coronarography have no clinical and/or ECG evidence for this diagnosis. The incidence of complex coronary lesions in this group is very low.

Tricuspid regurgitation in acute heart failure: is there any incremental risk?

Aim: Significant tricuspid regurgitation (TR) is common in heart failure (HF) and portends poor prognosis. We sought to determine whether the poor outcome results from the TR itself, or whether the TR is a surrogate marker of advanced left-sided myocardial or valvular heart disease. Methods and results: We studied 639 patients admitted for acute HF. The relationship between TR severity and the endpoint of readmission for HF or mortality was assessed after adjustment for multiple clinical and echocardiographic parameters. Higher TR grade was associated with higher congestion score and with other cardiac abnormalities including reduced left ventricular systolic function, moderate or severe mitral regurgitation, pulmonary hypertension (PH, defined as pulmonary artery systolic pressure ≥ 50 mmHg), and right ventricular dysfunction (all P < 0.001). Only 7% of patients with moderate or severe TR were free of other cardiac lesions. In adjusted models, moderate or severe TR was not associated with readmission for HF or mortality [hazard ratio (HR) 1.24, 95% confidence interval (95% CI) 0.97-1.57]. Patients with moderate/severe TR had similar risk for HF readmission or death compared with patients with trivial/mild TR when PH was not present (HR 1.17; 95% CI 0.78-1.75, P = 0.40) whereas the risk was higher in moderate/severe TR and PH (HR 1.78; 95% CI 1.34-2.36, P < 0.0001). Conclusion: Patients presenting with symptomatic HF and significant TR have multiple coexisting cardiac abnormalities. TR provides no additive risk in the presence of normal or mildly elevated pulmonary pressures. However, it is associated with excess rehospitalizations and mortality in patients with PH.

Usefulness of Pelvic Radiation Protection Shields During Transfemoral Procedures-Operator and Patient Considerations.

Interventional cardiologists are increasingly exposed to radiation-induced hazards. The MAVIG shield is a lead-free drape and the RADPAD is a sterile, disposable, and lead-free shield, placed on the patient with the aim to minimize operator-received scatter radiation. The objective of the trial was to examine their efficacy in a real-world situation. We randomized 125 patients who underwent coronary procedures from the right femoral artery into 3 groups: Control group (n = 48 [39%]) without additional protection, MAVIG lead shield (n = 38 [30%]) and RADPAD shield (n = 39 [31%]). Multiple radiation dosimeters were used in each case. All 3 groups were with similar baseline and procedural characteristics. Fluoroscopy time and number of views were similar in all 3 study groups. Compared with the standard (no shield) protection [3.5 ± 5.57 mSv], the scatter radiation was reduced by a factor of 5 for the MAVIG group [0.46 ± 1.6 mSv and p = 0.001] and a factor of 4 for the RADPAD group [1.16 ± 2.29 mSv and p = 0.01]. The physician's radiation decreased with the 2 shields, but only the MAVIG shield showed statistically significant lower radiation: 0.49 ± 0.42 mSv in the standard group versus 0.26 ± 0.3 mSv in the MAVIG and 0.35 ± 0.44 mSv in the RADPAD (p = 0.135 for RADPAD and p = 0.005 for MAVIG). Patient's exposure was statistically similar to the control group. Although numerically there was an increase in radiation with the RADPAD and decrease with the MAVIG. CONCLUSIONS: Our study found no statistically increase in patient radiation while the operator's radiation exposure was reduced. Decreasing scatter radiation can be done effectively using simple measurements and is of major importance.

Hyponatremia and long-term mortality in survivors of acute ST-elevation myocardial infarction.

BACKGROUND: Hyponatremia, a marker of neurohormonal activation, is a common electrolyte disorder among patients with acute ST-elevation myocardial infarction. The long-term prognostic value of hyponatremia during the acute phase of infarction is not known. METHODS: We studied 978 patients with acute ST-elevation myocardial infarction and without a history of heart failure who survived the index event. During the hospital stay, sodium levels were obtained on admission and at 24, 48, and 72 hours. The median duration of follow-up after hospital discharge was 31 months (range, 9-61 months). RESULTS: Hyponatremia, defined as a mean serum sodium level less than 136 mEq/L, was present during admission in 108 patients (11.0%). In a multivariable Cox proportional hazards model adjusting for other potential clinical predictors of mortality and for left ventricular ejection fraction, hyponatremia during admission remained an independent predictor of postdischarge death (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.3-3.2; P = .002). Hyponatremia during admission was also independently associated with postdischarge readmission for heart failure (HR, 1.6; 95% CI, 1.1-2.6; P = .04). When serum sodium level was used as a continuous variable, the adjusted HR for death or heart failure was 1.12 for every 1-mEq/L decrease (95% CI, 1.07-1.18; P<.001). CONCLUSION: Hyponatremia in the early phase of ST-elevation myocardial infarction is a predictor of long-term mortality and admission for heart failure after hospital discharge, independent of other clinical predictors of adverse outcome and left ventricular ejection fraction.

Transcatheter closure of a patent foramen ovale prior to a pneumonectomy to prevent platypnea syndrome.

An intracardiac shunt on an atrial level may be a cause of hypoxemia after lung surgery (platypnea-orthodeoxia syndrome). This syndrome may be successfully treated by percutaneous or surgical shunt closure. We present the case of preoperative transcatheter closure of a patent foramen ovale (PFO) for the prevention of possible platypnea after a forthcoming right pneumonectomy.

[Transcatheter treatment of combined congenital heart anomalies in an adult cyanotic patient].

Contemporary catheterization techniques allow effective percutaneous transcatheter treatment of congenital heart defects as an attractive alternative to open heart surgery. This case report describes transcatheter treatment of congenital pulmonary valve stenosis and secundum atrial septal defect which were diagnosed in a 31 year old woman who presented with cyanosis. This illustrates difficulties in the diagnosis of congenital heart disease in adult patients and demonstrates that transcatheter techniques in the treatment of these congenital anomalies are effective.

Time Dependence of the Effect of Right Ventricular Dysfunction on Clinical Outcomes After Myocardial Infarction: Role of Pulmonary Hypertension.

BACKGROUND: The clinical importance of right ventricular (RV) function in acute myocardial infarction is well recognized, but the impact of concomitant pulmonary hypertension (PH) has not been studied. METHODS AND RESULTS: We studied 1044 patients with acute myocardial infarction. Patients were classified into 4 groups according to the presence or absence of RV dysfunction and PH, defined as pulmonary artery systolic pressure >35 mm Hg: normal right ventricle without PH (n=509), normal right ventricle and PH (n=373), RV dysfunction without PH (n=64), and RV dysfunction and PH (n=98). A landmark analysis of early (admission to 30 days) and late (31 days to 8 years) mortality and readmission for heart failure was performed. In the first 30 days, RV dysfunction without PH was associated with a high mortality risk (adjusted hazard ratio 5.56, 95% CI 2.05-15.09, P<0.0001 compared with normal RV and no PH). In contrast, after 30 days, mortality rates among patients with RV dysfunction were increased only when PH was also present. Compared with patients having neither RV dysfunction nor PH, the adjusted hazard ratio for mortality was 1.44 (95% CI 0.68-3.04, P=0.34) in RV dysfunction without PH and 2.52 (95% CI 1.64-3.87, P<0.0001) in RV dysfunction with PH. PH with or without RV dysfunction was associated with increased risk for heart failure. CONCLUSION: In the absence of elevated pulmonary pressures, the risk associated with RV dysfunction after acute myocardial infarction is entirely confined to the first 30 days. Beyond 30 days, PH is the stronger risk factor for long-term mortality and readmission for heart failure.