Mark J. Ricciardi

Range of tricuspid regurgitation velocity at rest and during exercise in normal adult men: implications for the diagnosis of pulmonary hypertension☆

OBJECTIVES The aim of this study was to explore the full range of tricuspid valve regurgitation velocity (TRV) at rest and with exercise in disease free individuals. Additionally we examined the relationship of stroke volume (SV), cardiac output (CO) and TRV to exercise capacity. BACKGROUND Doppler evaluation of TRV can be used to estimate pulmonary artery systolic pressure (PASP). Most studies have assumed TRV < or = 2.5 m/s as the upper limits of normal. The full range of TRV with exercise has been incompletely defined. METHODS Highly conditioned athletes (n = 26) and healthy, active, young male volunteers (n = 14) underwent standardized recumbent bicycle exercise. Exercise parameters included: TRV, SV, CO, systolic (SBP) and diastolic (DBP) systemic blood pressure. RESULTS Tricuspid valve regurgitation, SV, HR and CO were significantly higher in athletes than in nonathletes over all workloads, including rest. Systolic blood pressure and DBP did not show significant differences between the two groups. CONCLUSIONS This study defines the upper physiologic limits of TRV at rest and during exercise in normals and provides a noninvasive standard for the diagnosis of pulmonary hypertension.

Inhaled nitric oxide in primary pulmonary hypertension : A safe and effective agent for predicting response to nifedipine

OBJECTIVES The purpose of this study was to assess the utility of inhaled nitric oxide (NO), a selective pulmonary vasodilator, for predicting the safety and acute hemodynamic response to high-dose oral nifedipine in primary pulmonary hypertension (PPH). BACKGROUND A significant decrease in pulmonary vascular resistance with an oral nifedipine challenge is predictive of an improved prognosis, and potential clinical efficacy in PPH. However, the required nifedipine trial carries significant first-dose risk of hypotension. While inhaled NO has been recommended for assessing pulmonary vasodilator reserve in PPH, it is not known whether it predicts the response to nifedipine. METHODS Seventeen patients with PPH undergoing a nifedipine trial were assessed for hemodynamic response to inhaled NO at 80 parts per million for 5 minutes. The nifedipine trial consisted of 20 mg of nifedipine hourly for 8 hours unless limited by hypotension or intolerable side effects. Patients were classified as responders and nonresponders with positive response defined as > or =20% reduction in mean pulmonary artery pressure (mPA) or pulmonary vascular resistance (PVR) with the vasodilator administration. RESULTS NO was safely administered to all participants. Seven of 17 (41.2%) responded to NO, and 8 of the 17 to nifedipine (47.1%). Nifedipine was safely administered in 14 of the 17. Three suffered either mild or severe hypotension, including one death. All NO responders also responded to nifedipine, and 9 of the 10 NO nonresponders were nifedipine nonresponders, representing a sensitivity of 87.5%, specificity of 100%, and overall predictive accuracy of 94%. All NO responders tolerated a full nifedipine trial without hypotension. There was a highly significant correlation between the effects of NO and nifedipine on PVR (r=0.67, p=0.003). CONCLUSIONS The pulmonary vascular response to inhaled NO accurately predicts the acute hemodynamic response to nifedipine in PPH, and a positive response to NO is associated with a safe nifedipine trial. In patients comparable with those evaluated, a trial of nifedipine in NO nonresponders appears unwarranted and potentially dangerous.

Concordant improvements in coronary flow reserve and ST-segment resolution during percutaneous coronary intervention for acute myocardial infarction: A benefit of postconditioning

Objective: To assess the effect of ischemic postconditioning on indices of coronary microvascular function during percutaneous coronary intervention (PCI) for acute ST segment elevation myocardial infarction (STEMI). Background: Myocardial tissue level perfusion remains suboptimal in many patients with STEMI despite restoration of antegrade flow in the epicardial coronary artery. Methods: Twenty‐four patients with an evolving anterior STEMI were randomized to undergo a previously‐validated ischemic postconditioning protocol or usual care during PCI. The extent of resolution of ST segment elevation along with Doppler‐tip catheter velocimetry was used as indices of myocardial reperfusion and microvascular function, respectively. Results: Postconditioned patients exhibited a greater, and therefore more rapid, extent of ST segment resolution (postconditioning, 70% ± 15%; control, 48% ± 16%; P = 0.0002) by the end of the procedure. Postconditioned patients also exhibited a greater hyperemic coronary vasodilator response at the completion of the procedure (coronary flow velocity reserve, CFVR: postconditioning, 2.2 ± 0.1; control, 1.5 ± 0.1; P < 0.0001). The end‐procedure CFVR was directly related to the extent of the ST segment resolution (r = 0.85) but inversely related to the absolute magnitude of ST segment elevation at end procedure (r = −0.76). Peak serum creatine kinase was significantly lower in postconditioned patients (postconditioning, 1,524 ± 435 IU/l; control, 1,862 ± 561 IU/l; P = 0.03). Conclusions: Ischemic postconditioning, as described, can be expeditiously performed during PCI for STEMI. Concordant changes in coronary flow reserve and ST segment resolution, measures of microcirculatory function, and myocardial perfusion, were greater in postconditioned patients.

Effect of tirofiban before primary angioplasty on initial coronary flow and early ST-segment resolution in patients with acute myocardial infarction.

Sixty-one patients with ST elevation acute myocardial infarction were randomized to receive open-label tirofiban in the emergency room before primary angioplasty versus glycoprotein IIb/IIIa inhibitors administered after initial coronary angiography. Early administration of tirofiban before primary angioplasty resulted in nonsignificant improvement in initial coronary flow (Thrombolysis In Myocardial Infarction trial grade 2 or 3 flow, 39% vs 27%, p >0.20). Patients receiving early tirofiban treatment were more likely to achieve complete (>70%) ST-segment resolution at 90 minutes (69% vs 44%, p = 0.07).

Angiographically silent left main disease detected by intravascular ultrasound: a marker for future adverse cardiac events

BACKGROUND Concomitant moderate obstructive left main (LM) disease is associated with future cardiac events and poor prognosis in patients undergoing percutaneous intervention (PCI). Whether prognosis is similarly effected by LM disease not detected by angiography, but evident on intravascular ultrasound (IVUS) imaging, is not known. The purpose of this study was to evaluate the long-term prognosis of patients with angiographically insignificant LM coronary artery disease undergoing PCI. METHODS AND RESULTS One hundred and seven consecutive patients undergoing PCI with angiographically normal or mild LM disease had 2- and 3-dimensional IVUS imaging. IVUS images were digitized, and 3-dimensional reconstruction was performed. Percent diameter and area stenosis by angiography were 4.8% +/- 3.5% and 18.2% +/- 9.8%, respectively. IVUS mean luminal area and area stenosis were 17.9 +/- 5.6 mm2 and 30.2% +/- 14.7%, respectively. Long-term follow-up was available in 102 (95%) patients at a median of 29 (range 8-52) months. Major adverse cardiac events, defined as death (6), myocardial infarction (4), repeat PCI (13), or CABG (16), were associated with female sex (P =.04), diabetes (P =.02), angiographic minimum lumen diameter (P =.04), and IVUS minimum (P =.01) and mean (P =.01) lumen area. Multivariate predictors of late cardiac events were diabetes (hazard ratio 2.69, P =.014) and minimum lumen area by IVUS (hazard ratio 0.59, P =.015). CONCLUSIONS Despite being angiographically silent, LM disease detected by IVUS is an independent predictor of cardiac events and may serve as a marker for such events. These data extend the spectrum of LM disease severity and its relationship to cardiac prognosis in patients undergoing PCI.

Myonecrosis following stent placement: association between impaired TIMI myocardial perfusion grade and MRI visualization of microinfarction.

Contrast‐enhanced cardiac MRI (ceMRI) and TIMI myocardial perfusion grade analysis (TMPG) are proven methods for visualization of microinfarction and assessment of microvascular perfusion, respectively. To determine whether microvascular obstruction accounts for procedure‐related myonecrosis, 14 poststent patients, 9 with procedural CK‐MB elevation and 5 controls, underwent ceMRI and TMPG. All had TIMI 3 flow pre‐ and poststent. TMPG was normal in 12/14 pre‐ and 7/14 poststent. Those with poststent decline in TMPG had higher CK‐MB (median, 41.0 vs. 7.4 ng/mL; P = 0.01) and larger infarct mass (median, 3.1 vs. 0.89 g; P = 0.04). More extensive myonecrosis (CK‐MB > 3 × normal; infarct mass > 3 g) was observed more frequently if there was a poststent decline in TMPG (3/3, 100%, vs. 2/11, 18.2%; P = 0.03). These data support the theory that distal embolization and microvascular obstruction are associated with myonecrosis following otherwise successful coronary stent placement and provide further insight into its pathophysiology. Catheter Cardiovasc Interv 2004;61:472–476.

Frequency, Predictors, and Appropriateness of Blood Transfusion After Percutaneous Coronary Interventions

Increased awareness of the risks of blood-borne infections has recently led to profound changes in the practice of transfusion medicine. These changes include, among others, the development of guidelines by the American College of Physicians (ACP) for transfusion. Although the incidence and predictors of vascular complications of percutaneous interventions have been well defined, there are currently no data on frequency, risk factors, and appropriateness of blood transfusions. We performed a retrospective analysis of 628 consecutive percutaneous coronary revascularization procedures. Predictors of blood transfusion were identified using multivariate logistic regression analysis. Appropriateness of transfusions was determined using modified ACP guidelines. Transfusions were administered after 8.9% of interventions (56 of 628). Multivariate analysis identified age >70 years, female gender, procedure duration, coronary stenting, acute myocardial infarction, postprocedural use of heparin and intra-aortic balloon pump placement as independent predictors of blood transfusions (all p <0.05). According to the ACP guidelines, 36 of 56 patients (64%) received transfusions inappropriately. Transfusion reactions (fever) occurred in 10% of patients who received tranfusions appropriately and in 5% of patients who received tranfusions inappropriately. The estimated additional costs per procedure related to transfusions were

Transcatheter Interatrial Shunt Device for the Treatment of Heart Failure With Preserved Ejection Fraction (REDUCE LAP-HF I [Reduce Elevated Left Atrial Pressure in Patients With Heart Failure]): A Phase 2, Randomized, Sham-Controlled Trial

551 and

Emergency Extracorporeal Membrane Oxygenation (ECMO)-Supported Percutaneous Coronary Interventions in the Fibrillating Heart

419, respectively. In conclusion, unnecessary transfusions were performed frequently after percutaneous coronary interventions. Application of available guidelines could reduce the number of unnecessary transfusions, thus avoiding exposure of patients to additional risks and reducing procedural costs.

Incidence and predictors of 30-day hospital readmission rate following percutaneous coronary intervention (from the National Heart, Lung, and Blood Institute Dynamic Registry).

Background: In nonrandomized, open-label studies, a transcatheter interatrial shunt device (IASD, Corvia Medical) was associated with lower pulmonary capillary wedge pressure (PCWP), fewer symptoms, and greater quality of life and exercise capacity in patients with heart failure (HF) and midrange or preserved ejection fraction (EF ≥40%). We conducted the first randomized sham-controlled trial to evaluate the IASD in HF with EF ≥40%. Methods: REDUCE LAP-HF I (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) was a phase 2, randomized, parallel-group, blinded multicenter trial in patients with New York Heart Association class III or ambulatory class IV HF, EF ≥40%, exercise PCWP ≥25 mm Hg, and PCWP-right atrial pressure gradient ≥5 mm Hg. Participants were randomized (1:1) to the IASD versus a sham procedure (femoral venous access with intracardiac echocardiography but no IASD placement). The participants and investigators assessing the participants during follow-up were blinded to treatment assignment. The primary effectiveness end point was exercise PCWP at 1 month. The primary safety end point was major adverse cardiac, cerebrovascular, and renal events at 1 month. PCWP during exercise was compared between treatment groups using a mixed-effects repeated measures model analysis of covariance that included data from all available stages of exercise. Results: A total of 94 patients were enrolled, of whom 44 met inclusion/exclusion criteria and were randomized to the IASD (n=22) and control (n=22) groups. Mean age was 70±9 years, and 50% were female. At 1 month, the IASD resulted in a greater reduction in PCWP compared with sham control (P=0.028 accounting for all stages of exercise). Peak PCWP decreased by 3.5±6.4 mm Hg in the treatment group versus 0.5±5.0 mm Hg in the control group (P=0.14). There were no peri-procedural or 1-month major adverse cardiac, cerebrovascular, and renal events in the IASD group and 1 event (worsening renal function) in the control group (P=1.0). Conclusions: In patients with HF and EF ≥40%, IASD treatment reduces PCWP during exercise. Whether this mechanistic effect will translate into sustained improvements in symptoms and outcomes requires further evaluation. Clinical Trial Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT02600234.